Sample records for opa1 mediate sequential

  1. Occupational physical activity and body mass index (BMI) among Canadian adults: does physical activity at work help to explain the socio-economic patterning of body weight?

    PubMed

    Barberio, Amanda; McLaren, Lindsay

    2011-01-01

    The behavioural and socio-cultural processes underlying the association between socio-economic position (SEP) and body mass index (BMI) remain unclear. Occupational physical activity (OPA) is one plausible explanatory variable that has not been previously considered. 1) To examine the association between OPA and BMI, and 2) to examine whether OPA mediates the SEP-BMI association, in a Canadian population-based sample. This cross-sectional study was based on secondary analysis of the 2008 Canadian Community Health Survey data, focusing on adults (age 25-64) working at a job or business (men, n = 1,036; women, n = 936). BMI was based on measured height and weight and we derived a novel indicator of OPA from the National Occupational Classification Career Handbook. Our analytic technique was ordinary least squares regression, adjusting for a range of socio-demographic, health and behavioural covariates. OPA was marginally associated with BMI in women, such that women with medium levels of OPA tended to be lighter than women with low levels of OPA, in adjusted models. No associations between OPA and BMI were detected for males. Baron and Kenny's (1986) three conditions for testing mediation were not satisfied, and thus we were unable to proceed with testing OPA as a mediator. Notwithstanding the small effects observed in women, overall the associations between OPA and BMI were neither clear nor strong, which could reflect conceptual and/or methodological reasons. Future research on this topic might incorporate other plausible explanatory variables (e.g., job-related psychosocial stress) and adopt a prospective design.

  2. Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease.

    PubMed

    Granoff, Dan M

    2009-06-24

    Killing of Neisseria meningitidis can result from complement-mediated serum bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers > or =1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers > or =1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease.

  3. Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease

    PubMed Central

    Granoff, Dan M.

    2009-01-01

    Killing of Neisseria meningitidis can result from complement-mediated bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers ≥1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers ≥1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease. PMID:19477054

  4. Loss of Drp1 function alters OPA1 processing and changes mitochondrial membrane organization

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

    Moepert, Kristin; Hajek, Petr; Frank, Stephan

    2009-08-01

    RNAi mediated loss of Drp1 function changes mitochondrial morphology in cultured HeLa and HUVEC cells by shifting the balance of mitochondrial fission and fusion towards unopposed fusion. Over time, inhibition of Drp1 expression results in the formation of a highly branched mitochondrial network along with 'bulge'-like structures. These changes in mitochondrial morphology are accompanied by a reduction in levels of Mitofusin 1 (Mfn1) and 2 (Mfn2) and a modified proteolytic processing of OPA1 isoforms, resulting in the inhibition of cell proliferation. In addition, our data imply that bulge formation is driven by Mfn1 action along with particular proteolytic short-OPA1 (s-OPA1)more » variants: Loss of Mfn2 in the absence of Drp1 results in an increase of Mfn1 levels along with processed s-OPA1-isoforms, thereby enhancing continuous 'fusion' and bulge formation. Moreover, bulge formation might reflect s-OPA1 mitochondrial membrane remodeling activity, resulting in the compartmentalization of cytochrome c deposits. The proteins Yme1L and PHB2 appeared not associated with the observed enhanced OPA1 proteolysis upon RNAi of Drp1, suggesting the existence of other OPA1 processing controlling proteins. Taken together, Drp1 appears to affect the activity of the mitochondrial fusion machinery by unbalancing the protein levels of mitofusins and OPA1.« less

  5. Broad anti-HIV activity of the Oscillatoria agardhii agglutinin homologue lectin family.

    PubMed

    Férir, Geoffrey; Huskens, Dana; Noppen, Sam; Koharudin, Leonardus M I; Gronenborn, Angela M; Schols, Dominique

    2014-10-01

    Oscillatoria agardhii agglutinin homologue (OAAH) proteins belong to a recently discovered lectin family. The founding member OAA and a designed hybrid OAAH (OPA) recognize similar but unique carbohydrate structures of Man-9, compared with other antiviral carbohydrate-binding agents (CBAs). These two newly described CBAs were evaluated for their inactivating properties on HIV replication and transmission and for their potential as microbicides. Various cellular assays were used to determine antiviral activity against wild-type and certain CBA-resistant HIV-1 strains: (i) free HIV virion infection in human T lymphoma cell lines and PBMCs; (ii) syncytium formation assay using persistently HIV-infected T cells and non-infected CD4+ T cells; (iii) DC-SIGN-mediated viral capture; and (iv) transmission to uninfected CD4+ T cells. OAA and OPA were also evaluated for their mitogenic properties and potential synergistic effects using other CBAs. OAA and OPA inhibit HIV replication, syncytium formation between HIV-1-infected and uninfected T cells, DC-SIGN-mediated HIV-1 capture and transmission to CD4+ target T cells, thereby rendering a variety of HIV-1 and HIV-2 clinical isolates non-infectious, independent of their coreceptor use. Both CBAs competitively inhibit the binding of the Manα(1-2)Man-specific 2G12 monoclonal antibody (mAb) as shown by flow cytometry and surface plasmon resonance analysis. The HIV-1 NL4.3(2G12res), NL4.3(MVNres) and IIIB(GRFTres) strains were equally inhibited as the wild-type HIV-1 strains by these CBAs. Combination studies indicate that OAA and OPA act synergistically with Hippeastrum hybrid agglutinin, 2G12 mAb and griffithsin (GRFT), with the exception of OPA/GRFT. OAA and OPA are unique CBAs with broad-spectrum anti-HIV activity; however, further optimization will be necessary for microbicidal application. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. In vivo adaptation and persistence of Neisseria meningitidis within the nasopharyngeal mucosa.

    PubMed

    Johswich, Kay O; McCaw, Shannon E; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E; Gray-Owen, Scott D

    2013-01-01

    Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa.

  7. In Vivo Adaptation and Persistence of Neisseria meningitidis within the Nasopharyngeal Mucosa

    PubMed Central

    Johswich, Kay O.; McCaw, Shannon E.; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E.; Gray-Owen, Scott D.

    2013-01-01

    Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa. PMID:23935487

  8. Irritancy and Allergic Responses Induced by Exposure to the Indoor Air Chemical 4-Oxopentanal

    PubMed Central

    Anderson, Stacey E.; Franko, Jennifer; Jackson, Laurel G.; Wells, J. R.; Ham, Jason E.; Meade, B. J.

    2012-01-01

    Over the last two decades, there has been an increasing awareness regarding the potential impact of indoor air pollution on human health. People working in an indoor environment often experience symptoms such as eye, nose, and throat irritation. Investigations into these complaints have ascribed the effects, in part, to compounds emitted from building materials, cleaning/consumer products, and indoor chemistry. One suspect indoor air contaminant that has been identified is the dicarbonyl 4-oxopentanal (4-OPA). 4-OPA is generated through the ozonolysis of squalene and several high-volume production compounds that are commonly found indoors. Following preliminary workplace sampling that identified the presence of 4-OPA, these studies examined the inflammatory and allergic responses to 4-OPA following both dermal and pulmonary exposure using a murine model. 4-OPA was tested in a combined local lymph node assay and identified to be an irritant and sensitizer. A Th1-mediated hypersensitivity response was supported by a positive response in the mouse ear swelling test. Pulmonary exposure to 4-OPA caused a significant elevation in nonspecific airway hyperreactivity, increased numbers of lung-associated lymphocytes and neutrophils, and increased interferon-γ production by lung-associated lymph nodes. These results suggest that both dermal and pulmonary exposure to 4-OPA may elicit irritant and allergic responses and may help to explain some of the adverse health effects associated with poor indoor air quality. PMID:22403157

  9. Reactions of hypoiodous acid with model compounds and the formation of iodoform in absence/presence of permanganate.

    PubMed

    Zhao, Xiaodan; Ma, Jun; von Gunten, Urs

    2017-08-01

    The kinetics for the reactions of hypoiodous acid (HOI) with various phenols (phenol, 4-nitrophenol, 4-hydroxybenzoic acid), 3-oxopentanedioic acid (3-OPA) and flavone were investigated in the pH range of 6.0-11.0. The apparent second order rate constants for the reactions of HOI with phenolic compounds, 3-OPA, flavone and citric acid at pH 8.0 are 10-10 7  M -1 s -1 , (4.0 ± 0.3) × 10 3  M -1 s -1 , (2.5 ± 0.2) × 10 3  M -1 s -1 and <1 M -1 s -1 , respectively. The effect of buffer type and concentration was investigated with acetate, phosphate and borate. All tested buffers promote the HOI reactions with phenols. The percentage of iodine incorporation for various (hydroxyl)phenolic compounds and two NOM extracts ranges from 5% to 98%, indicating that electrophilic aromatic substitution and/or electron transfer can occur. The extent of these reactions depends on the number and relative position of the hydroxyl moieties on the phenolic compounds. Iodoform formation rates increase with increasing pH and iodoform yields increase from 9% to 67% for pH 6.0-10.0 for the HOI/3-OPA reactions. In the permanganate/HOI/3-OPA and permanganate/iodide/3-OPA system at pH < 8.0, iodoform formation is elevated compared to the HOI/3-OPA system in absence of permanganate. For pH > 8.0, in presence of permanganate, iodoform formation is significantly inhibited and iodate formation enhanced, which is due to a faster permanganate-mediated HOI disproportionation to iodate compared to the iodination process. The production of reactive iodine in real waters containing iodide in contact with permanganate may lead to the formation of iodinated organic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Genetic Screening for OPA1 and OPA3 Mutations in Patients with Suspected Inherited Optic Neuropathies

    PubMed Central

    Yu-Wai-Man, Patrick; Shankar, Suma P.; Biousse, Valérie; Miller, Neil R.; Bean, Lora J.H.; Coffee, Bradford; Hegde, Madhuri; Newman, Nancy J.

    2010-01-01

    Purpose Autosomal-dominant optic atrophy (DOA) is one of the most common inherited optic neuropathies, and it is genetically heterogeneous, with mutations in both OPA1 and OPA3 known to cause disease. About 60% of cases harbor OPA1 mutations, whereas OPA3 mutations have only been reported in two pedigrees with DOA and premature cataracts. The aim of this study was to determine the yield of OPA1 and OPA3 screening in a cohort of presumed DOA cases referred to a tertiary diagnostic laboratory. Design Retrospective case series. Participants One hundred and eighty-eight probands with bilateral optic atrophy referred for molecular genetic investigations at a tertiary diagnostic facility: 38 patients with an autosomal-dominant pattern of inheritance and 150 sporadic cases. Methods OPA1 and OPA3 genetic testing was initially performed using PCR-based sequencing methods. The presence of large-scale OPA1 and OPA3 genomic rearrangements was further assessed with a targeted comparative genomic hybridization (CGH) microarray platform. The three primary Leber hereditary optic neuropathy (LHON) mutations, m.3460G>A, m.11778G>A, and m.14484T>C, were also screened in all patients. Main Outcome Measures The proportion of patients with OPA1 and OPA3 pathogenic mutations. The clinical profile observed in molecularly confirmed DOA cases. Results We found 21 different OPA1 mutations in 27 of the 188 (14.4%) probands screened. The mutations included six novel pathogenic variants and the first reported OPA1 initiation codon mutation at c.1A>T. An OPA1 missense mutation, c.239A>G (p.Y80C), was identified in an 11-year-old African-American girl with optic atrophy and peripheral sensori-motor neuropathy in her lower limbs. The OPA1 detection rate was significantly higher among individuals with a positive family history of visual failure (50.0%) compared with sporadic cases (5.3%). The primary LHON screen was negative in our patient cohort, and additional molecular investigations did not reveal any large-scale OPA1 rearrangements or OPA3 genetic defects. The mean baseline visual acuity for our OPA1-positive group was 0.48 logarithm of the minimum angle of resolution (LogMAR) (Mean Snellen equivalent = 20/61, range = 20/20–20/400, 95% confidence interval = 20/52–20/71), and visual deterioration occurred in 54.2% of patients during follow-up. Conclusions OPA1 mutations are the most common genetic defects identified in patients with suspected DOA, whereas OPA3 mutations are very rare in isolated optic atrophy cases. PMID:21036400

  11. m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

    PubMed

    Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

    2018-04-09

    The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

  12. Diagnostic genetic testing for patients with bilateral optic neuropathy and comparison of clinical features according to OPA1 mutation status.

    PubMed

    Gaier, Eric D; Boudreault, Katherine; Nakata, Isao; Janessian, Maria; Skidd, Philip; DelBono, Elizabeth; Allen, Keri F; Pasquale, Louis R; Place, Emily; Cestari, Dean M; Stacy, Rebecca C; Rizzo, Joseph F; Wiggs, Janey L

    2017-01-01

    Inherited optic neuropathy is genetically heterogeneous, and genetic testing has an important role in risk assessment and counseling. The purpose of this study is to determine the prevalence and spectrum of mutations in a group of patients referred for genetic testing to a tertiary center in the United States. In addition, we compared the clinical features of patients with and without mutations in OPA1 , the gene most commonly involved in dominantly inherited optic atrophy. Clinical data and genetic testing results were reviewed for 74 unrelated, consecutive patients referred with a history of insidious, relatively symmetric, bilateral visual loss secondary to an optic neuropathy. Patients were evaluated for disease-causing variants in OPA1 , OPA3 , WFS1 , and the entire mitochondrial genome with DNA sequencing and copy number variation (CNV) testing. Pathogenic DNA variants were found in 25 cases, with the majority (24 patients) located in OPA1 . Demographics, clinical history, and clinical features for the group of patients with mutations in OPA1 were compared to those without disease-causing variants. Compared to the patients without mutations, cases with mutations in OPA1 were more likely to have a family history of optic nerve disease (p = 0.027); however, 30.4% of patients without a family history of disease also had mutations in OPA1 . OPA1 mutation carriers had less severe mean deviation and pattern standard deviation on automated visual field testing than patients with optic atrophy without mutations in OPA1 (p<0.005). Other demographic and ocular features were not statistically significantly different between the two groups, including the fraction of patients with central scotomas (42.9% of OPA1 mutation positive and 66.0% of OPA1 mutation negative). Genetic testing identified disease-causing mutations in 34% of referred cases, with the majority of these in OPA1. Patients with mutations in OPA1 were more likely to have a family history of disease; however, 30.4% of patients without a family history were also found to have an OPA1 mutation. This observation, as well as similar frequencies of central scotomas in the groups with and without mutations in OPA1 , underscores the need for genetic testing to establish an OPA1 genetic diagnosis.

  13. Common variants of OPA1 conferring genetic susceptibility to leprosy in Han Chinese from Southwest China.

    PubMed

    Xiang, Yang-Lin; Zhang, Deng-Feng; Wang, Dong; Li, Yu-Ye; Yao, Yong-Gang

    2015-11-01

    Leprosy is an ancient chronic infection caused by Mycobacterium leprae. Onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of M. leprae. The optic atrophy 1 (OPA1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity. To investigate the potential involvement of OPA1 in leprosy. We analyzed 7 common genetic variants of OPA1 in 1110 Han Chinese subjects with and without leprosy, followed by mRNA expression profiling and protein-protein interaction (PPI) network analysis. We observed positive associations between OPA1 variants rs9838374 (Pgenotypic=0.003) and rs414237 (Pgenotypic=0.002) with lepromatous leprosy. expression quantitative trait loci (eQTL) analysis showed that the leprosy-related risk allele C of rs414237 is correlated with lower OPA1 mRNA expression level. Indeed, we identified a decrease of OPA1 mRNA expression in both with patients and cellular model of leprosy. In addition, the PPI analysis showed that OPA1 protein was actively involved in the interaction network of M. leprae induced differentially expressed genes. Our results indicated that OPA1 variants confer risk of leprosy and may affect OPA1 expression, mitochondrial function and antimicrobial pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Loss of Prohibitin Membrane Scaffolds Impairs Mitochondrial Architecture and Leads to Tau Hyperphosphorylation and Neurodegeneration

    PubMed Central

    Merkwirth, Carsten; Morbin, Michela; Brönneke, Hella S.; Jordan, Sabine D.; Rugarli, Elena I.; Langer, Thomas

    2012-01-01

    Fusion and fission of mitochondria maintain the functional integrity of mitochondria and protect against neurodegeneration, but how mitochondrial dysfunctions trigger neuronal loss remains ill-defined. Prohibitins form large ring complexes in the inner membrane that are composed of PHB1 and PHB2 subunits and are thought to function as membrane scaffolds. In Caenorhabditis elegans, prohibitin genes affect aging by moderating fat metabolism and energy production. Knockdown experiments in mammalian cells link the function of prohibitins to membrane fusion, as they were found to stabilize the dynamin-like GTPase OPA1 (optic atrophy 1), which mediates mitochondrial inner membrane fusion and cristae morphogenesis. Mutations in OPA1 are associated with dominant optic atrophy characterized by the progressive loss of retinal ganglion cells, highlighting the importance of OPA1 function in neurons. Here, we show that neuron-specific inactivation of Phb2 in the mouse forebrain causes extensive neurodegeneration associated with behavioral impairments and cognitive deficiencies. We observe early onset tau hyperphosphorylation and filament formation in the hippocampus, demonstrating a direct link between mitochondrial defects and tau pathology. Loss of PHB2 impairs the stability of OPA1, affects mitochondrial ultrastructure, and induces the perinuclear clustering of mitochondria in hippocampal neurons. A destabilization of the mitochondrial genome and respiratory deficiencies manifest in aged neurons only, while the appearance of mitochondrial morphology defects correlates with tau hyperphosphorylation in the absence of PHB2. These results establish an essential role of prohibitin complexes for neuronal survival in vivo and demonstrate that OPA1 stability, mitochondrial fusion, and the maintenance of the mitochondrial genome in neurons depend on these scaffolding proteins. Moreover, our findings establish prohibitin-deficient mice as a novel genetic model for tau pathologies caused by a dysfunction of mitochondria and raise the possibility that tau pathologies are associated with other neurodegenerative disorders caused by deficiencies in mitochondrial dynamics. PMID:23144624

  15. Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control.

    PubMed

    Glytsou, Christina; Calvo, Enrique; Cogliati, Sara; Mehrotra, Arpit; Anastasia, Irene; Rigoni, Giovanni; Raimondi, Andrea; Shintani, Norihito; Loureiro, Marta; Vazquez, Jesùs; Pellegrini, Luca; Enriquez, Jose Antonio; Scorrano, Luca; Soriano, Maria Eugenia

    2016-12-13

    The mitochondrial contact site and cristae organizing system (MICOS) and Optic atrophy 1 (OPA1) control cristae shape, thus affecting mitochondrial function and apoptosis. Whether and how they physically and functionally interact is unclear. Here, we provide evidence that OPA1 is epistatic to MICOS in the regulation of cristae shape. Proteomic analysis identifies multiple MICOS components in native OPA1-containing high molecular weight complexes disrupted during cristae remodeling. MIC60, a core MICOS protein, physically interacts with OPA1, and together, they control cristae junction number and stability, OPA1 being epistatic to MIC60. OPA1 defines cristae width and junction diameter independently of MIC60. Our combination of proteomics, biochemistry, genetics, and electron tomography provides a unifying model for mammalian cristae biogenesis by OPA1 and MICOS. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Contribution of organized and nonorganized activity to children's motor skills and fitness.

    PubMed

    Hardy, Louise L; O'Hara, Blythe J; Rogers, Kris; St George, Alexis; Bauman, Adrian

    2014-11-01

    To examine the associations between children's organized physical activity (OPA), nonorganized physical activity (NOPA), and health-related outcomes (fundamental movement skill [FMS] fitness). Cross-sectional survey of children aged 10-16 years (N = 4273). Organized physical activity and NOPA were assessed by self-report, FMS by process-orientated criteria, and fitness by 20-m shuttle run test. Boys spent 97.5 minutes and girls 86.6 minutes in daily physical activity with the majority spent in OPA (boys, 56.3%; girls 60.5%). Organized physical activity increased with grade, whereas NOPA decreased. Organized physical activity and NOPA were associated with fitness, and OPA was consistently associated with FMS competency. Boys' fitness was associated with OPA and NOPA (adjusted odds ratio [AOR] 1.42, 95% confidence interval [CI]: 1.04, 1.94; AOR 1.26, 95% CI: 1.03, 1.54, respectively), FMS competency (side gallop leap, kick) with OPA and catch, and over-arm throw with both OPA and NOPA. Girls' fitness (AOR 2.62, 95% CI: 1.88, 3.66) and FMS competency were consistently associated with OPA. Both OPA and NOPA are important contributors to children's physical activity; however, for girls, OPA was more strongly associated with fitness and FMS competency. Our findings support the importance of providing children with opportunities to engage in daily OPA. School physical education programs are an ideal delivery vehicle for OPA and need to be central to education policy. © 2014, American School Health Association.

  17. A recurrent deletion mutation in OPA1 causes autosomal dominant optic atrophy in a Chinese family

    NASA Astrophysics Data System (ADS)

    Zhang, Liping; Shi, Wei; Song, Liming; Zhang, Xiao; Cheng, Lulu; Wang, Yanfang; Ge, Xianglian; Li, Wei; Zhang, Wei; Min, Qingjie; Jin, Zi-Bing; Qu, Jia; Gu, Feng

    2014-11-01

    Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy.

  18. A recurrent deletion mutation in OPA1 causes autosomal dominant optic atrophy in a Chinese family.

    PubMed

    Zhang, Liping; Shi, Wei; Song, Liming; Zhang, Xiao; Cheng, Lulu; Wang, Yanfang; Ge, Xianglian; Li, Wei; Zhang, Wei; Min, Qingjie; Jin, Zi-Bing; Qu, Jia; Gu, Feng

    2014-11-06

    Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy.

  19. PGAM5 regulates PINK1/Parkin-mediated mitophagy via DRP1 in CCCP-induced mitochondrial dysfunction.

    PubMed

    Park, Yun Sun; Choi, Su Eun; Koh, Hyun Chul

    2018-03-01

    Mitochondrial dynamics and mitophagy are critical processes for regulating mitochondrial homeostasis. Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein that plays crucial roles in apoptosis and necroptosis, but the roles of PGAM5 in mitochondrial dynamics and mitophagy remain unclear. In this study, we investigated the role of PGAM5 in carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced mitochondrial damage and the correlation between mitochondrial dynamics and mitophagy using SH-SY5Y cells. We found that CCCP decreased mitochondrial membrane potential, resulting in mitochondrial dysfunction. CCCP increased PGAM5, dynamin-related protein 1 (DRP1), and optic atrophy 1 (OPA1) expression of the mitochondrial fraction in a time-dependent manner. Knockdown of PGAM5 inhibited DRP1 translocation without a change in OPA1 expression in CCCP-treated cells. Furthermore, knockdown of PGAM5 and DRP1 significantly blocked the increase of PTEN-induced putative protein kinase 1 (PINK1) and Parkin expression in the mitochondrial fraction of CCCP-treated cells. Interestingly, CCCP did not alter PINK1/Parkin expression in the mitochondrial fraction of OPA1 knockdown cells. Inhibiting mitophagy by PGAM5 knockdown accelerated CCCP-induced apoptosis. CCCP treatment also results in PINK1 stabilization on the mitochondrial membrane, which subsequently increases Parkin recruitment from the cytosol to abnormal mitochondria. In addition, we found that CCCP increased the level of mitochondrial LC3II, indicating that Parkin recruitment of PINK1 is a result of mitophagy. We propose that activation of PGAM5 is associated with DRP1 recruitment and PINK1 stabilization, which contribute to the modulation of mitophagy in CCCP-treated cells with mitochondrial dysfunction. In conclusion, we demonstrated that PGAM5 regulates PINK1-Parkin-mediated mitophagy, which can exert a neuroprotective effect against CCCP-induced apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model

    PubMed Central

    Fauconnier, Jérémy; Cellier, Laura; Tamareille, Sophie; Gharib, Abdallah; Chevrollier, Arnaud; Loufrani, Laurent; Grenier, Céline; Kamel, Rima; Sarzi, Emmanuelle; Lacampagne, Alain; Ovize, Michel; Henrion, Daniel; Reynier, Pascal; Lenaers, Guy; Mirebeau-Prunier, Delphine

    2016-01-01

    Background Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain. Objectives To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries. Methods and Results We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates. Cardiac left-ventricular systolic function assessed by means of echocardiography was observed to be similar in 3-month-old WT and Opa1+/- mice. After subjection to I/R, infarct size was significantly greater in Opa1+/- than in WTs both in vivo (43.2±4.1% vs. 28.4±3.5%, respectively; p<0.01) and ex vivo (71.1±3.2% vs. 59.6±8.5%, respectively; p<0.05). No difference was observed in the expression of other main fission/fusion protein, oxidative phosphorylation, apoptotic markers, or mitochondrial permeability transition pore (mPTP) function. Analysis of calcium transients in isolated ventricular cardiomyocytes demonstrated a lower sarcoplasmic reticulum Ca2+ uptake, whereas cytosolic Ca2+ removal from the Na+/Ca2+ exchanger (NCX) was increased, whilst SERCA2a, phospholamban, and NCX protein expression levels were unaffected in Opa1+/- compared to WT mice. Simultaneous whole-cell patch-clamp recordings of mitochondrial Ca2+ movements and ventricular action potential (AP) showed impairment of dynamic mitochondrial Ca2+ uptake and a marked increase in the AP late repolarization phase in conjunction with greater occurrence of arrhythmia in Opa1+/- mice. Conclusion Opa1 deficiency was associated with increased sensitivity to I/R, imbalance in dynamic mitochondrial Ca2+ uptake, and subsequent increase in NCX activity. PMID:27723783

  1. Occupational physical activity, but not leisure-time physical activity increases the risk of atrial fibrillation: The Copenhagen City Heart Study.

    PubMed

    Skielboe, Ane K; Marott, Jacob L; Dixen, Ulrik; Friberg, Jens B; Jensen, Gorm B

    2016-11-01

    Previous findings regarding physical activity and risk of incident atrial fibrillation (AF) are controversial, focusing on leisure-time physical activity (LTPA) and without distinguishing it from occupational physical activity (OPA). Our aim was to study the association between physical activity and risk of AF, with special attention to the possible divergent effects of OPA and LTPA. In a prospective, observational cohort study, 17,196 subjects were included from the Copenhagen Population Register. All participants had a physical examination, a 12-lead electrocardiogram (ECG), and answered a questionnaire regarding health and physical activity. Participants without previously diagnosed AF who answered adequately regarding OPA and LTPA were included. LTPA and OPA were each graded into four levels. Follow-up were carried out between 1981-1983, 1991-1994, and 2001-2003. Information regarding hospitalization and mortality was drawn from the National Patient Registry and the Registry of Causes of Death. Outcome was incident AF as determined by follow-up ECG or register diagnosis. In univariable Cox regression analysis all sub-groups of OPA had a significant higher risk of AF compared to moderate OPA. When adjusting for confounders, the risk remained significantly increased for high OPA (hazard ratio (HR) 1.21 (95% confidence interval (CI) 1.02-1.43), p = 0.028), and very high OPA (HR 1.39 (95% CI 1.03-1.88), p = 0.034). We found no significant association between LTPA and incident AF. High and very high OPA were associated with a significantly increased risk of incident AF. LTPA was not associated with risk of incident AF. © The European Society of Cardiology 2016.

  2. Advanced laser architectures for high power eyesafe illuminators

    NASA Astrophysics Data System (ADS)

    Baranova, N.; Pati, B.; Stebbins, K.; Bystryak, I.; Rayno, M.; Ezzo, K.; DePriest, C.

    2018-02-01

    Q-Peak has demonstrated a novel pulsed eyesafe laser architecture operating with >50 mJ pulse energies at Pulse Repetition Frequencies (PRFs) as high as 320 Hz. The design leverages an Optical Parametric Oscillator (OPO) and Optical Parametric Amplifier (OPA) geometry, which provides the unique capability for high power in a comparatively compact package, while also offering the potential for additional eyesafe power scaling. The laser consists of a Commercial Off-the-Shelf (COTS) Q-switched front-end seed laser to produce pulse-widths around 10 ns at 1.06-μm, which is then followed by a pair of Multi-Pass Amplifier (MPA) architectures (comprised of side-pumped, multi-pass Nd:YAG slabs with a compact diode-pump-array imaging system), and finally involving two sequential nonlinear optical conversion architectures for transfer into the eyesafe regime. The initial seed beam is first amplified through the MPA, and then split into parallel optical paths. An OPO provides effective nonlinear conversion on one optical path, while a second MPA further amplifies the 1.06-μm beam for use in pumping an OPA on the second optical path. These paths are then recombined prior to seeding the OPA. Each nonlinear conversion subsystem utilizes Potassium Titanyl Arsenate (KTA) for effective nonlinear conversion with lower risk to optical damage. This laser architecture efficiently produces pulse energies of >50 mJ in the eyesafe band at PRFs as high as 320 Hz, and has been designed to fit within a volume of 4,500 in3 (0.074 m3 ). We will discuss theoretical and experimental details of the nonlinear optical system for achieving higher eyesafe powers.

  3. Inner membrane fusion mediates spatial distribution of axonal mitochondria

    PubMed Central

    Yu, Yiyi; Lee, Hao-Chih; Chen, Kuan-Chieh; Suhan, Joseph; Qiu, Minhua; Ba, Qinle; Yang, Ge

    2016-01-01

    In eukaryotic cells, mitochondria form a dynamic interconnected network to respond to changing needs at different subcellular locations. A fundamental yet unanswered question regarding this network is whether, and if so how, local fusion and fission of individual mitochondria affect their global distribution. To address this question, we developed high-resolution computational image analysis techniques to examine the relations between mitochondrial fusion/fission and spatial distribution within the axon of Drosophila larval neurons. We found that stationary and moving mitochondria underwent fusion and fission regularly but followed different spatial distribution patterns and exhibited different morphology. Disruption of inner membrane fusion by knockdown of dOpa1, Drosophila Optic Atrophy 1, not only increased the spatial density of stationary and moving mitochondria but also changed their spatial distributions and morphology differentially. Knockdown of dOpa1 also impaired axonal transport of mitochondria. But the changed spatial distributions of mitochondria resulted primarily from disruption of inner membrane fusion because knockdown of Milton, a mitochondrial kinesin-1 adapter, caused similar transport velocity impairment but different spatial distributions. Together, our data reveals that stationary mitochondria within the axon interconnect with moving mitochondria through fusion and fission and that local inner membrane fusion between individual mitochondria mediates their global distribution. PMID:26742817

  4. Macular Pigment Optical Density and Ocular Pulse Amplitude in Subjects with Different Axial Lengths and Refractive Errors.

    PubMed

    Czepita, Maciej; Karczewicz, Danuta; Safranow, Krzysztof; Czepita, Damian

    2015-06-13

    The purpose of our study was to: (1) investigate the macular pigment optical density (MPOD) and ocular pulse amplitude (OPA) in subjects with different axial lengths (AL) and refractive errors (RE); (2) determine if there is a correlation between MPOD and OPA; and (3) evaluate whether MPOD and OPA depend on intraocular pressure (IOP). This study included 140 eyes of 70 subjects - 17 men and 53 women, aged 18 to 29 years (mean: 22.5 years; SD=2.8). Every examined person underwent a thorough eye examination including: visual acuity, anterior segment and fundus examination, keratometry, auto-refractometry, and MPOD, OPA, AL, and IOP measurements. The obtained results were analyzed statistically using Statistica 10 software. P values of <0.05 were considered statistically significant. The following refractive errors were selected: emmetropia (34 eyes), hyperopia (18 eyes), low myopia (60 eyes), medium myopia (19 eyes), and high myopia (9 eyes). It has been established that the OPA increases with the rise in the spherical equivalents (SE) (Rs=+0.38, P<0.001), while the increase in AL correlates with the decrease of OPA (Rs=-0.40, P<0.001). The increase in IOP correlates with the rise in the OPA (Rs=+0.20, P<0.05). There were no significant correlations between IOP and SE or AL. (1) MPOD is not correlated with the OPA in subjects with different AL and RE; (2) OPA decreases with the rise of AL; (3) OPA decreases with the fall of the SE; and (4) OPA increases with the rise in IOP.

  5. Demonstration of an optical phased array using electro-optic polymer phase shifters

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshikuni; Motoyama, Yasushi; Tanaka, Katsu; Machida, Kenji; Yamada, Toshiki; Otomo, Akira; Kikuchi, Hiroshi

    2018-03-01

    We have been investigating an optical phased array (OPA) using electro-optic (EO) polymers in phase shifters to achieve ultrafast optical beam steering. In this paper, we describe the basic structures of the OPA using EO polymer phase shifters and show the beam steering capability of the OPA. The designed OPA has a multimode interference (MMI) beam splitter and 8-channel polymer waveguides with EO polymer phase shifters. We compare 1 × 8 MMI and cascaded 1 × 2 MMI beam splitters numerically and experimentally, and then obtain uniform intensity outputs from the 1 × 8 beam splitter. We fabricate the EO polymer OPA with a 1 × 8 MMI beam splitter to prevent intensity dispersion due to radiation loss in bending waveguides. We also evaluate the optical beam steering capability of the fabricated OPA and found a 2.7° deflection of far-field patterns when applying a voltage difference of 25 V in adjacent phase shifters.

  6. Comparison of Ocular Pulse Amplitude Lowering Effects of Preservative-Free Tafluprost and Preservative-Free Dorzolamide-Timolol Fixed Combination Eyedrops.

    PubMed

    Seo, Du Ri; Ha, Seung Joo

    2015-01-01

    To compare the ocular pulse amplitude (OPA) lowering effects of preservative-free tafluprost and dorzolamide-timolol fixed combination (DTFC) using dynamic contour tonometry. In total, 66 eyes of 66 patients with normal tension glaucoma (NTG) (n = 34) or primary open angle glaucoma (POAG) (n = 32) were included. Patients were divided into two groups: the preservative-free tafluprost-treated group (n = 33) and the preservative-free DTFC-treated group (n = 33). Intraocular pressure (IOP) was measured using Goldmann applanation tonometry (GAT). OPA was measured using dynamic contour tonometry; corrected OPA (cOPA) was calculated at baseline and at 1 week and 1, 3, and 6 months after treatment. After 6 months of treatment, tafluprost significantly reduced IOP (P < 0.001). The OPA lowering effects differed significantly between the two treatment groups (P = 0.003). The cOPA-lowering effect of tafluprost (1.09 mmHg) was significantly greater than that of DTFC (0.36 mmHg) after 6 months of treatment (P = 0.01). Tafluprost and DTFC glaucoma treatments provided marked OPA and IOP lowering effects. Tafluprost had a greater effect than DTFC; thus, this drug is recommended for patients at risk of glaucoma progression, due to the high OPA caused by large fluctuations in IOP.

  7. Antibiotic Resistance In Neisseria Gonorrhoeae: Impact Of Ceftriaxone Resistance On Microbial Fitness And Potential Of Resistance Determinants To Spread During Mixed Infection

    DTIC Science & Technology

    2016-03-07

    14 1.4d Antibacterial Drug Resistance .......................................................................... 17 1.4d1 Modification of the...Depending upon receptor engagement, Opa-mediated interactions can either activate the innate immune system via neutrophil activation or suppress the...himself was never able to develop the antibacterial mold he had discovered into a mass-produced antibiotic for human use, efforts by scientists in

  8. Does influence at work modify the relation between high occupational physical activity and risk of heart disease in women?

    PubMed

    Allesøe, Karen; Holtermann, Andreas; Rugulies, Reiner; Aadahl, Mette; Boyle, Eleanor; Søgaard, Karen

    2017-07-01

    To investigate whether influence at work modifies the association between demanding and strenuous occupational physical activity (OPA) and risk of ischaemic heart disease (IHD). A sample of 12,093 nurses aged 45-64 years from the Danish Nurse Cohort Study was followed for 20.6 years by individual linkage to incident IHD in the Danish National Patient Registry. Information on OPA, influence at work, other occupational factors and known risk factors for IHD was collected by self-report in 1993. During follow-up 869 nurses were hospitalised with incident IHD. Nurses exposed to strenuous OPA and low influence at work had a 46% increased risk of IHD [hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.02-2.09)] compared to the reference group of nurses with moderate OPA and high influence at work. Nurses exposed to strenuous OPA and high influence at work were not at an increased risk of IHD [HR 1.10 (95% CI 0.59-2.06)]. An additive hazards model showed there were 18.0 (95% CI -0.01 to 36.0) additional cases of IHD per 10,000 person years among nurses with strenuous OPA and low influence at work compared to nurses with moderate OPA and high influence at work. A detrimental additive interaction between strenuous OPA and low influence at work that could explain the additional cases of IHD among nurses with strenuous OPA and low influence at work was indicated. The findings suggest that high influence at work may buffer some of the adverse effects of strenuous OPA on risk of IHD.

  9. Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis.

    PubMed

    Millet, Aurélie M C; Bertholet, Ambre M; Daloyau, Marlène; Reynier, Pascal; Galinier, Anne; Devin, Anne; Wissinguer, Bernd; Belenguer, Pascale; Davezac, Noélie

    2016-06-01

    OPA1 mutations cause protein haploinsufficiency leading to dominant optic atrophy (DOA), an incurable retinopathy with variable severity. Up to 20% of patients also develop extraocular neurological complications. The mechanisms that cause this optic atrophy or its syndromic forms are still unknown. After identifying oxidative stress in a mouse model of the pathology, we sought to determine the consequences of OPA1 dysfunction on redox homeostasis. Mitochondrial respiration, reactive oxygen species levels, antioxidant defenses, and cell death were characterized by biochemical and in situ approaches in both in vitro and in vivo models of OPA1 haploinsufficiency. A decrease in aconitase activity suggesting an increase in reactive oxygene species and an induction of antioxidant defenses was observed in cortices of a murine model as well as in OPA1 downregulated cortical neurons. This increase is associated with a decline in mitochondrial respiration in vitro. Upon exogenous oxidative stress, OPA1-depleted neurons did not further exhibit upregulated antioxidant defenses but were more sensitive to cell death. Finally, low levels of antioxidant enzymes were found in fibroblasts from patients supporting their role as modifier factors. Our study suggests that the pro-oxidative state induced by OPA1 loss may contribute to DOA pathogenesis and that differences in antioxidant defenses can explain the variability in expressivity. Furthermore, antioxidants may be used as therapy as they could prevent or delay DOA symptoms in patients.

  10. Elevated hydrostatic pressure triggers release of OPA1 and cytochrome C, and induces apoptotic cell death in differentiated RGC-5 cells

    PubMed Central

    Kim, Keun-Young; Lindsey, James D.; Angert, Mila; Patel, Ankur; Scott, Ray T.; Liu, Quan; Crowston, Jonathan G.; Ellisman, Mark H.; Perkins, Guy A.; Weinreb, Robert N.

    2009-01-01

    Purpose This study was conducted to determine whether elevated hydrostatic pressure alters mitochondrial structure, triggers release of the dynamin-related guanosine triphosphatase (GTPase) optic atrophy type 1 (OPA1) or cytochrome C from mitochondria, alters OPA1 gene expression, and can directly induce apoptotic cell death in cultured retinal ganglion cell (RGC)-5 cells. Methods Differentiated RGC-5 cells were exposed to 30 mmHg for three days in a pressurized incubator. As a control, differentiated RGC-5 cell cultures were incubated simultaneously in a conventional incubator. Live RGC-5 cells were then labeled with MitoTracker Red and mitochondrial morphology was assessed by fluorescence microscopy. Mitochondrial structural changes were also assessed by electron microscopy and three-dimenstional (3D) electron microscope tomography. OPA1 mRNA was measured by Taqman quantitative PCR. The cellular distribution of OPA1 protein and cytochrome C was assessed by immunocytochemistry and western blot. Caspase-3 activation was examined by western blot. Apoptotic cell death was evaluated by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results Mitochondrial fission, characterized by the conversion of tubular fused mitochondria into isolated small organelles, was triggered after three days exposure to elevated hydrostatic pressure. Electron microscopy confirmed the fission and noted no changes to mitochondrial architecture, nor outer membrane rupture. Electron microscope tomography showed that elevated pressure depleted mitochondrial cristae content by fourfold. Elevated hydrostatic pressure increased OPA1 gene expression by 35±14% on day 2, but reduced expression by 36±4% on day 3. Total OPA1 protein content was not changed on day 2 or 3. However, pressure treatment induced release of OPA1 and cytochrome C from mitochondria to the cytoplasm. Elevated pressure also activated caspase-3 and induced apoptotic cell death. Conclusions Elevated hydrostatic pressure triggered mitochondrial changes including mitochondrial fission and abnormal cristae depletion, alteration of OPA1 gene expression, and release of OPA1 and cytochrome C into the cytoplasm before the onset of apoptotic cell death in differentiated RGC-5 cells. These results suggest that sustained moderate pressure elevation may directly damage RGC integrity by injuring mitochondria. PMID:19169378

  11. Mitochondrial remodeling following fission inhibition by 15d-PGJ2 involves molecular changes in mitochondrial fusion protein OPA1

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

    Kar, Rekha; Department of Biochemistry, UT Health Science Center at San Antonio, San Antonio, TX 78229; Mishra, Nandita

    2010-09-03

    Research highlights: {yields} Chemical inhibition of fission protein Drp1 leads to mitochondrial fusion. {yields} Increased fusion stimulates molecular changes in mitochondrial fusion protein OPA1. {yields} Proteolysis of larger isoforms, new synthesis and ubiquitination of OPA1 occur. {yields} Loss of mitochondrial tubular rigidity and disorganization of cristae. {yields} Generation of large swollen dysfunctional mitochondria. -- Abstract: We showed earlier that 15 deoxy {Delta}{sup 12,14} prostaglandin J2 (15d-PGJ2) inactivates Drp1 and induces mitochondrial fusion . However, prolonged incubation of cells with 15d-PGJ2 resulted in remodeling of fused mitochondria into large swollen mitochondria with irregular cristae structure. While initial fusion of mitochondria bymore » 15d-PGJ2 required the presence of both outer (Mfn1 and Mfn2) and inner (OPA1) mitochondrial membrane fusion proteins, later mitochondrial changes involved increased degradation of the fusion protein OPA1 and ubiquitination of newly synthesized OPA1 along with decreased expression of Mfn1 and Mfn2, which likely contributed to the loss of tubular rigidity, disorganization of cristae, and formation of large swollen degenerated dysfunctional mitochondria. Similar to inhibition of Drp1 by 15d-PGJ2, decreased expression of fission protein Drp1 by siRNA also resulted in the loss of fusion proteins. Prevention of 15d-PGJ2 induced mitochondrial elongation by thiol antioxidants prevented not only loss of OPA1 isoforms but also its ubiquitination. These findings provide novel insights into unforeseen complexity of molecular events that modulate mitochondrial plasticity.« less

  12. Irritancy and Allergic Responses Induced by Topical Application of ortho-Phthalaldehyde

    PubMed Central

    Anderson, Stacey E.; Umbright, Christina; Sellamuthu, Rajendran; Fluharty, Kara; Kashon, Michael; Franko, Jennifer; Jackson, Laurel G.; Johnson, Victor J.; Joseph, Pius

    2010-01-01

    Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG1. In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde. PMID:20176622

  13. Direct fluorescence characterisation of a picosecond seeded optical parametric amplifier

    NASA Astrophysics Data System (ADS)

    Stuart, N. H.; Bigourd, D.; Hill, R. W.; Robinson, T. S.; Mecseki, K.; Patankar, S.; New, G. H. C.; Smith, R. A.

    2015-02-01

    The temporal intensity contrast of high-power lasers based on optical parametric amplification (OPA) can be limited by parametric fluorescence from the non-linear gain stages. Here we present a spectroscopic method for direct measurement of unwanted parametric fluorescence widely applicable from unseeded to fully seeded and saturated OPA operation. Our technique employs simultaneous spectroscopy of fluorescence photons slightly outside the seed bandwidth and strongly attenuated light at the seed central wavelength. To demonstrate its applicability we have characterised the performance of a two-stage picosecond OPA pre-amplifier with 2.8×105 gain, delivering 335 μJ pulses at 1054 nm. We show that fluorescence from a strongly seeded OPA is reduced by ~500× from the undepleted to full pump depletion regimes. We also determine the vacuum fluctuation driven noise term seeding this OPA fluorescence to be 0.7±0.4 photons ps-1 nm-1 bandwidth. The resulting shot-to-shot statistics highlights a 1.5% probability of a five-fold and 0.3% probability of a ten-fold increase of fluorescence above the average value. Finally, we show that OPA fluorescence can be limited to a few-ps pedestal with 3×10-9 temporal intensity contrast 1.3 ps ahead of an intense laser pulse, a level highly attractive for large scale chirped-pulse OPA laser systems.

  14. Dominant optic atrophy.

    PubMed

    Lenaers, Guy; Hamel, Christian; Delettre, Cécile; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal; Milea, Dan

    2012-07-09

    DEFINITION OF THE DISEASE: Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Patients are usually diagnosed during their early childhood, because of bilateral, mild, otherwise unexplained visual loss related to optic discs pallor or atrophy, and typically occurring in the context of a family history of DOA. Optical Coherence Tomography further discloses non-specific thinning of retinal nerve fiber layer, but a normal morphology of the photoreceptors layers. Abnormal visual evoked potentials and pattern ERG may also reflect the dysfunction of the RGCs and their axons. Molecular diagnosis is provided by the identification of a mutation in the OPA1 gene (75% of DOA patients) or in the OPA3 gene (1% of patients). Visual loss in DOA may progress during puberty until adulthood, with very slow subsequent chronic progression in most of the cases. On the opposite, in DOA patients with associated extra-ocular features, the visual loss may be more severe over time. To date, there is no preventative or curative treatment in DOA; severely visually impaired patients may benefit from low vision aids. Genetic counseling is commonly offered and patients are advised to avoid alcohol and tobacco consumption, as well as the use of medications that may interfere with mitochondrial metabolism. Gene and pharmacological therapies for DOA are currently under investigation.

  15. Dominant optic atrophy

    PubMed Central

    2012-01-01

    Definition of the disease Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of bilateral, mild, otherwise unexplained visual loss related to optic discs pallor or atrophy, and typically occurring in the context of a family history of DOA. Optical Coherence Tomography further discloses non-specific thinning of retinal nerve fiber layer, but a normal morphology of the photoreceptors layers. Abnormal visual evoked potentials and pattern ERG may also reflect the dysfunction of the RGCs and their axons. Molecular diagnosis is provided by the identification of a mutation in the OPA1 gene (75% of DOA patients) or in the OPA3 gene (1% of patients). Prognosis Visual loss in DOA may progress during puberty until adulthood, with very slow subsequent chronic progression in most of the cases. On the opposite, in DOA patients with associated extra-ocular features, the visual loss may be more severe over time. Management To date, there is no preventative or curative treatment in DOA; severely visually impaired patients may benefit from low vision aids. Genetic counseling is commonly offered and patients are advised to avoid alcohol and tobacco consumption, as well as the use of medications that may interfere with mitochondrial metabolism. Gene and pharmacological therapies for DOA are currently under investigation. PMID:22776096

  16. Intensity and temporal noise characteristics in femtosecond optical parametric amplifiers.

    PubMed

    Chen, Wei; Fan, Jintao; Ge, Aichen; Song, Huanyu; Song, Youjian; Liu, Bowen; Chai, Lu; Wang, Chingyue; Hu, Minglie

    2017-12-11

    We characterize the relative intensity noise (RIN) and relative timing jitter (RTJ) between the signal and pump pulses of optical parametric amplifiers (OPAs) seeded by three different seed sources. Compared to a white-light continuum (WLC) seeded- and an optical parametric generator (OPG) seeded OPA, the narrowband CW seeded OPA exhibits the lowest root-mean-square (RMS) RIN and RTJ of 0.79% and 0.32 fs, respectively, integrated from 1 kHz to the Nyquist frequency of 1.25 MHz. An improved numerical model based on a forward Maxwell equation (FME) is built to investigate the transfers of the pump and seed's noise to the resulting OPAs' intensity and temporal fluctuation. Both the experimental and numerical study indicate that the low level of noise from the narrowband CW seeded OPA is attributed to the elimination of the RIN and RTJ coupled from the noise of seed source, being one of the important contributions to RIN and timing jitter in the other two OPAs. The approach to achieve lower level of noise from this CW seeded OPA by driving it close to saturation is also discussed with the same numerical model.

  17. Occupational and leisure-time physical activity and risk of disability pension: prospective data from the HUNT Study, Norway

    PubMed Central

    Fimland, Marius Steiro; Vie, Gunnhild; Holtermann, Andreas; Krokstad, Steinar; Nilsen, Tom Ivar Lund

    2018-01-01

    Objectives To prospectively investigate the association between occupational physical activity (OPA) and disability pension due to musculoskeletal cause, mental cause or any cause. We also examined the combined association of OPA and leisure-time physical activity (LTPA) with disability pension. Methods A population-based cohort study in Norway on 32 362 persons aged 20–65 years with questionnaire data on OPA and LTPA that were followed up for incident disability pension through the National Insurance Database. We used Cox regression to estimate adjusted HRs with 95% CIs. Results During a follow-up of 9.3 years, 3837 (12%) received disability pension. Compared with people with mostly sedentary work, those who performed much walking, much walking and lifting, and heavy physical work had HRs of 1.26 (95% CI 1.16 to 1.38), 1.44 (95% CI 1.32 to 1.58) and 1.48 (95% CI 1.33 to 1.70), respectively. These associations were stronger for disability pension due to musculoskeletal disorders, whereas there was no clear association between OPA and risk of disability pension due to mental disorders. People with high OPA and low LTPA had a HR of 1.77 (95% CI 1.58 to 1.98) for overall disability pension and HR of 2.56 (95% CI 2.10 to 3.11) for disability pension due to musculoskeletal disorders, versus low OPA and high LTPA. Conclusions We observed a positive association between OPA and risk of disability pension due to all causes and musculoskeletal disorders, but not for mental disorders. Physical activity during leisure time reduced some, but not all of the unfavourable effect of physically demanding work on risk of disability pension. PMID:28698178

  18. U.S. Coast Guard 1995 oil pollution research grants publications : part 1

    DOT National Transportation Integrated Search

    1997-08-01

    The Oil Pollution Research Grants Program was created by the Oil Pollution Act (OPA) of 1990, P.L. 101-380 (OPA 90), 33 U.S.C. 28761(c)(8) and 2761(c)(9). The OPA established a regional research program and authorized those agencies represented on th...

  19. Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

    PubMed

    Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

    2017-02-01

    Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

  20. The investigation of the interaction between piracetam and bovine serum albumin by spectroscopic methods

    NASA Astrophysics Data System (ADS)

    Guo, Xingjia; Han, Xiaowei; Tong, Jian; Guo, Chuang; Yang, Wenfeng; Zhu, Jifen; Fu, Bing

    2010-03-01

    The interaction between piracetam (OPA) with bovine serum albumin (BSA) has been thoroughly studied by fluorescence quenching technique in combination with UV-vis absorption, Fourier transform infrared (FT-IR), and circular dichroism (CD) spectroscopies under the simulative physiological conditions. The quenching of BSA fluorescence by OPA was found to be a static quenching process. The binding constants ( K a) are 3.014, 2.926, and 2.503 × 10 3 M -1 at 292, 298, and 309 K, respectively. According to the van't Hoff equation, the thermodynamic functions standard enthalpy (Δ H) and standard entropy (Δ S) for the reaction were calculated to be -74.560 kJ mol -1 and -159.380 J mol -1 K -1, which indicated that OPA binds to BSA mainly by hydrogen bonds and van der Waals interactions. The binding distance between BSA and OPA was calculated to be 4.10 nm according to the theory of FÖrster's non-radiation energy transfer. The displacement experiments confirmed that OPA could bind to the site I of BSA. Furthermore, the effects of pH and some common ions on the binding constant were also examined. And the alterations of protein secondary structure in the presence of OPA were observed by the CD and FT-IR spectra.

  1. In situ interactions between Opalinus Clay and Low Alkali Concrete

    NASA Astrophysics Data System (ADS)

    Lerouge, Catherine; Gaboreau, Stéphane; Grangeon, Sylvain; Claret, Francis; Warmont, Fabienne; Jenni, Andreas; Cloet, Veerle; Mäder, Urs

    2017-06-01

    A five-year-old interface between a Low Alkali Concrete (LAC) formulation (CEM III/B containing 66% slag and 10% nano-silica) and Opalinus Clay (OPA) from a field experiment at Mont Terri Underground Rock Laboratory in Switzerland (Jenni et al., 2014) has been studied to decipher the textural, mineralogical and chemical changes that occurred between the two reacting materials. Reactivity between LAC concrete and OPA is found to be limited to a ∼1 mm thick highly porous (ca. 75% porosity) white crust developed on the concrete side. Quantitative mineralogical mapping of the white crust using an electron microprobe and infrared spectroscopy on the cement matrix provides evidence of a Mg-rich phase accounting for approximatively 25 wt % of the matrix associated with 11 wt % of calcite, calcium silicate hydrate (C-S-H) and other cement phases. EDX analyses and electron diffraction combined with transmission electron microscopy of the Mg-rich phase provide evidence for a tri-octahedral 2:1 phyllosilicate with mean composition: (Ca0.5±0.2) (Mg2.0±0.4, Fe0.2±0.1, Al0.5±03, □0.3±0.3) (Al0.9±0.2, Si3.1±0.2) O10 (OH)2, where □ represents vacancies in the octahedral site. Apart from this reactive contact, textural, mineralogical and chemical modifications at the contact with the LAC concrete are limited. OPA mineralogy remains largely unmodified. X-ray micro-fluorescence and EPMA mapping of major elements on the OPA side also provides evidence for a Mg-enriched 300-400 μm thick layer. The cation exchange capacity (CEC) values measured in the OPA in contact with the LAC concrete range between 153 and 175 meq kg-1 of dry OPA, close to the reference value of 170 ± 10 meq kg-1 of dry OPA (Pearson et al., 2003). Changing cation occupancies at the interface with LAC concrete are mainly marked by increased Ca, Mg and K, and decreased Na. Leaching tests performed on OPA with deionized water and at different solid to water ratios strongly suggest that Cl and SO4 have either conservative behaviour or are constrained by the solubility of a precipitated sulfate phase. The Cl and SO4 concentrations measured at 2 cm from the interface are close to concentrations of undisturbed OPA pore waters (SO4: 4.5 ± 1.5 mmol kg-1 of dry OPA; Cl: 7.5 ± 2.1 mmol kg-1of dry OPA), and increase towards the interface with the concrete. The SO4 to Cl ratio also increases towards the interface, suggesting that the increasing anion concentrations are not related to porosity variations but rather to a concentration gradient and sulfate phase precipitation near the interface.

  2. Occupational physical activity, overweight, and mortality: a follow-up study of 47,405 Norwegian women and men.

    PubMed

    Graff-Iversen, Sidsel; Selmer, Randi; Sørensen, Marit; Skurtveit, Svetlana

    2007-06-01

    This population-based 24-year follow-up study evaluated the association of occupational physical activity (OPA) with overweight and mortality in 47,405 men and women, healthy at baseline, and reporting OPA as sedentary (reference), light, moderately heavy, or heavy. The adjusted odds ratio for overweight was slightly less than 1 for all categories of current nonsedentary work in men but increased by OPA in women. Only heavy OPA conferred a lower mortality with an adjusted rate ratio of 0.84 (95 % confidence interval, 0.76-0.92) for men and 0.69 (95 % confidence interval, 0.52-0.91) for women. This observational study, with OPA recorded in the 1970s and 1980s, suggested a slight protective effect for overweight by nonsedentary work for men and lower mortality by heavy OPA for both genders.

  3. Novel Applications for Oxalate-Phosphate-Amine Metal-Organic-Frameworks (OPA-MOFs): Can an Iron-Based OPA-MOF Be Used as Slow-Release Fertilizer?

    PubMed Central

    Anstoetz, Manuela; Rose, Terry J.; Clark, Malcolm W.; Yee, Lachlan H.; Raymond, Carolyn A.; Vancov, Tony

    2015-01-01

    A porous iron-based oxalate-phosphate-amine metal-organic framework material (OPA-MOF) was investigated as a microbially-induced slow-release nitrogen (N) and phosphorus (P) fertilizer. Seedling growth, grain yields, nutrient uptake of wheat plants, and soil dynamics in incubated soil, were investigated using OPA-MOF vs standard P (triple-superphosphate) and N (urea) fertilizers in an acidic Ferralsol at two application rates (equivalent 120 and 40 kg N ha-1). While urea hydrolysis in the OPA-MOF treatment was rapid, conversion of ammonium to nitrate was significantly inhibited compared to urea treatment. Reduced wheat growth in OPA-MOF treatments was not caused by N-deficiency, but by limited P-bioavailability. Two likely reasons were slow P-mobilisation from the OPA-MOF or rapid P-binding in the acid soil. P-uptake and yield in OPA-MOF treatments were significantly higher than in nil-P controls, but significantly lower than in conventionally-fertilised plants. OPA-MOF showed potential as enhanced efficiency N fertilizer. However, as P-bioavailability was insufficient to meet plant demands, further work should determine if P-availability may be enhanced in alkaline soils, or whether central ions other than Fe, forming the inorganic metal-P framework in the MOF, may act as a more effective P-source in acid soils. PMID:26633174

  4. Novel Applications for Oxalate-Phosphate-Amine Metal-Organic-Frameworks (OPA-MOFs): Can an Iron-Based OPA-MOF Be Used as Slow-Release Fertilizer?

    PubMed

    Anstoetz, Manuela; Rose, Terry J; Clark, Malcolm W; Yee, Lachlan H; Raymond, Carolyn A; Vancov, Tony

    2015-01-01

    A porous iron-based oxalate-phosphate-amine metal-organic framework material (OPA-MOF) was investigated as a microbially-induced slow-release nitrogen (N) and phosphorus (P) fertilizer. Seedling growth, grain yields, nutrient uptake of wheat plants, and soil dynamics in incubated soil, were investigated using OPA-MOF vs standard P (triple-superphosphate) and N (urea) fertilizers in an acidic Ferralsol at two application rates (equivalent 120 and 40 kg N ha(-1)). While urea hydrolysis in the OPA-MOF treatment was rapid, conversion of ammonium to nitrate was significantly inhibited compared to urea treatment. Reduced wheat growth in OPA-MOF treatments was not caused by N-deficiency, but by limited P-bioavailability. Two likely reasons were slow P-mobilisation from the OPA-MOF or rapid P-binding in the acid soil. P-uptake and yield in OPA-MOF treatments were significantly higher than in nil-P controls, but significantly lower than in conventionally-fertilised plants. OPA-MOF showed potential as enhanced efficiency N fertilizer. However, as P-bioavailability was insufficient to meet plant demands, further work should determine if P-availability may be enhanced in alkaline soils, or whether central ions other than Fe, forming the inorganic metal-P framework in the MOF, may act as a more effective P-source in acid soils.

  5. Deformation mechanisms and evolution of the microstructure of gouge in the Main Fault in Opalinus Clay in the Mont Terri rock laboratory (CH)

    NASA Astrophysics Data System (ADS)

    Laurich, Ben; Urai, Janos L.; Vollmer, Christian; Nussbaum, Christophe

    2018-01-01

    We studied gouge from an upper-crustal, low-offset reverse fault in slightly overconsolidated claystone in the Mont Terri rock laboratory (Switzerland). The laboratory is designed to evaluate the suitability of the Opalinus Clay formation (OPA) to host a repository for radioactive waste. The gouge occurs in thin bands and lenses in the fault zone; it is darker in color and less fissile than the surrounding rock. It shows a matrix-based, P-foliated microfabric bordered and truncated by micrometer-thin shear zones consisting of aligned clay grains, as shown with broad-ion-beam scanning electron microscopy (BIB-SEM) and optical microscopy. Selected area electron diffraction based on transmission electron microscopy (TEM) shows evidence for randomly oriented nanometer-sized clay particles in the gouge matrix, surrounding larger elongated phyllosilicates with a strict P foliation. For the first time for the OPA, we report the occurrence of amorphous SiO2 grains within the gouge. Gouge has lower SEM-visible porosity and almost no calcite grains compared to the undeformed OPA. We present two hypotheses to explain the origin of gouge in the Main Fault: (i) authigenic generation consisting of fluid-mediated removal of calcite from the deforming OPA during shearing and (ii) clay smear consisting of mechanical smearing of calcite-poor (yet to be identified) source layers into the fault zone. Based on our data we prefer the first or a combination of both, but more work is needed to resolve this. Microstructures indicate a range of deformation mechanisms including solution-precipitation processes and a gouge that is weaker than the OPA because of the lower fraction of hard grains. For gouge, we infer a more rate-dependent frictional rheology than suggested from laboratory experiments on the undeformed OPA.

  6. Occupational and leisure-time physical activity and risk of disability pension: prospective data from the HUNT Study, Norway.

    PubMed

    Fimland, Marius Steiro; Vie, Gunnhild; Holtermann, Andreas; Krokstad, Steinar; Nilsen, Tom Ivar Lund

    2018-01-01

    To prospectively investigate the association between occupational physical activity (OPA) and disability pension due to musculoskeletal cause, mental cause or any cause. We also examined the combined association of OPA and leisure-time physical activity (LTPA) with disability pension. A population-based cohort study in Norway on 32 362 persons aged 20-65 years with questionnaire data on OPA and LTPA that were followed up for incident disability pension through the National Insurance Database. We used Cox regression to estimate adjusted HRs with 95% CIs. During a follow-up of 9.3 years, 3837 (12%) received disability pension. Compared with people with mostly sedentary work, those who performed much walking, much walking and lifting, and heavy physical work had HRs of 1.26 (95% CI 1.16 to 1.38), 1.44 (95% CI 1.32 to 1.58) and 1.48 (95% CI 1.33 to 1.70), respectively. These associations were stronger for disability pension due to musculoskeletal disorders, whereas there was no clear association between OPA and risk of disability pension due to mental disorders. People with high OPA and low LTPA had a HR of 1.77 (95% CI 1.58 to 1.98) for overall disability pension and HR of 2.56 (95% CI 2.10 to 3.11) for disability pension due to musculoskeletal disorders, versus low OPA and high LTPA. We observed a positive association between OPA and risk of disability pension due to all causes and musculoskeletal disorders, but not for mental disorders. Physical activity during leisure time reduced some, but not all of the unfavourable effect of physically demanding work on risk of disability pension. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Effect of sub-Tenon's and peribulbar anesthesia on intraocular pressure and ocular pulse amplitude.

    PubMed

    Pianka, P; Weintraub-Padova, H; Lazar, M; Geyer, O

    2001-08-01

    To compare the effect of peribulbar and sub-Tenon's anesthesia on intraocular pressure (IOP) and ocular pulse amplitude (OPA) in the injected eye and the fellow noninjected (control) eye. Tel Aviv Medical Center, Tel Aviv, Israel. This prospective study measured IOP and OPA at baseline and 1 and 10 minutes after administration of lidocaine anesthesia in 40 consecutive adult patients having elective cataract surgery. The IOP remained stable throughout the study with both modes of anesthesia. One minute after injection of the anesthetic agent, the OPA was significantly decreased in the injected eyes in both the sub-Tenon's (24%; P < .05) and peribulbar (25%; P < .05) groups. The decrease in the OPA in the sub-Tenon's group (14%; P < .05) was detectable after 10 minutes in the control eyes. In the peribulbar anesthesia group, the OPA in the control eyes increased significantly (9%; P < .05) 1 minute after injection of the anesthetic agent, returning to preinjection levels 10 minutes after the injection. The OPA in the eyes in which lidocaine was injected decreased significantly in both the sub-Tenon's and peribulbar groups. These findings have implications for the management of patients whose ocular circulation may be compromised.

  8. Assay for optical determination of biogenic amines using microtiterplates

    NASA Astrophysics Data System (ADS)

    Nedeljko, Polona; Turel, Matejka; Lobnik, Aleksandra

    2013-05-01

    Direct determination of catecholamine noradreanaline (NOR) is presented using o-phthaldialdehyde (OPA) as an indicator reagent. The fluorescent assay in which OPA forms with NOR a fluorescent complex (OPA-NOR) can be monitored at neutral, physiological conditions (pH 7) and performed in microtiterplates. The determination of NOR is optimal in the concentration range from 4.0×10-7 to 1.0×10-5 M and limit of detection is 4.0×10-7 M. The OPA-NOR complex maximum intensity is reached within 5 minutes. Dopamine and adrenaline could not be determined using the same approach.

  9. Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial.

    PubMed

    Frakking, Thuy T; Chang, Anne B; O'Grady, Kerry-Ann F; Walker-Smith, Katie; Weir, Kelly A

    2013-11-07

    Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of 'CFE + CA' versus 'CFE' only compared to MBS-identified OPA. Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785.

  10. Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785. PMID:24199872

  11. Effect of quantifying peptide release on ruminal protein degradation determined using the inhibitor in vitro system.

    PubMed

    Colombini, S; Broderick, G A; Clayton, M K

    2011-04-01

    The aim of this work was to compare use of an o-phthaldialdehyde (OPA) colorimetric assay (OPA-C), which responds to both free AA and peptides, with an OPA fluorimetric assay (OPA-F), which is insensitive to peptides, to quantify rates of ruminal protein degradation in the inhibitor in vitro system using Michaelis-Menten saturation kinetics. Four protein concentrates (expeller-extracted soybean meal, ESBM; 2 solvent-extracted soybean meals, SSBM1 and SSBM2; and casein) were incubated in a ruminal in vitro system treated with hydrazine and chloramphenicol to inhibit microbial uptake of protein degradation products. Proteins were weighed to give a range of N concentrations (from 0.15 to 3 mg of N/mL of inoculum) and incubated with 10 mL of ruminal inoculum and 5 mL of buffer; fermentations were stopped after 2 h by adding trichloroacetic acid (TCA). Proteins were analyzed for buffer-soluble N and buffer extracts were treated with TCA to determine N degraded at t=0 (FD0). The TCA supernatants were analyzed for ammonia (phenol-hypochlorite assay), total AA (TAA; OPA-F), and TAA plus oligopeptides (OPA-C) by flow injection analysis. Velocity of protein degradation was computed from extent of release of 1) ammonia plus free TAA or 2) ammonia plus free TAA and peptides. Rate of degradation (kd) was quantified using nonlinear regression of the integrated Michaelis-Menten equation. The parameters Km (Michaelis constant) and kd (Vmax/Km), where Vmax=maximum velocity, were estimated directly; kd values were adjusted (Akd) for the fraction FD0 using the equation Akd=kd-FD0/2. The OPA-C assay yielded faster degradation rates due to the contribution of peptides to the fraction degraded (overall mean=0.280/h by OPA-C and 0.219/h by OPA-F). Degradation rates for SSBM samples (0.231/h and 0.181/h) and ESBM (0.086/h) obtained by the OPA-C assay were more rapid than rates reported by the National Research Council (NRC). Both assays indicated that the 2 SSBM differed in rumen-undegradable protein (RUP) content; the more slowly degraded SSBM had RUP content (35% by OPA-C) similar to that reported by the NRC. The RUP content of ESBM (42% by OPA-C) was lower than the NRC value. Preliminary studies with 4 additional protein concentrates confirmed that accounting for peptide formation increased degradation rate; however, a trend for an interaction between assay and protein source suggested that peptide release made a smaller contribution to rate for more slowly degraded proteins. The OPA-C assay is a simple and reliable method to quantify formation of small peptides. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Inhibition of TNFα-induced adhesion molecule expression by (Z)-(S)-9-octadecenamide, N-(2-hydroxyethyl,1-methyl).

    PubMed

    Chen, Caixia; Jin, Xin; Meng, Xianglan; Zheng, Chengwei; Shen, Yanhui; Wang, Yiqing

    2011-06-25

    Inflammation is a primary event in atherogenesis. Oleoylethanolamide (OEA), a naturally occurring fatty-acid ethanolamide, lowers lipid levels in liver and blood through activation of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPARα). We designed and synthesized (Z)-(S)-9-octadecenamide, N-(2-hydroxyethyl, 1-methyl) (OPA), an OEA analog. The present study investigated the effect of OPA on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVEC). OPA inhibited expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) stimulated by Tumor Necrosis Factor-α (TNF-α) via activation of PPARα. This inhibition of VCAM-1 and ICAM-1 expression decreased adhesion of monocyte-like cells to stimulated endothelial cells. These results demonstrate that OPA may have anti-inflammatory properties. Our results thus provide new insights into possible future therapeutic approaches to the treatment of atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Potential Protective Mechanism in the Cardiac Microvascular Injury.

    PubMed

    Li, Xiuchuan; Hou, Juanni; Du, Jin; Feng, Jian; Yang, Yi; Shen, Yang; Chen, Sha; Feng, Juan; Yang, Dachun; Li, De; Pei, Haifeng; Yang, Yongjian

    2018-05-07

    Cardiac microvascular injury often occurs in patients with type 2 diabetes mellitus (T2DM) who develop hyperglycemia and hyperlipidemia. However, besides reported contradictory roles in cardiac diseases, the function of TRPV1 (transient receptor potential vanilloid 1) in cardiac microvessels is not well defined. This study was performed to determine the detailed role of TRPV1 in cardiac microvascular endothelial cells (CMECs) in T2DM. T2DM mice were established by multiple injections of low-dose streptozotocin and high-fat feeding. CMECs were cultured separately in mediums of normal glucose, high glucose (HG), high fatty acid (HF), and HG plus HF (HG-HF). HG-HF inhibited TRPV1 expression in CMECs, reducing cellular Ca 2+ content ([Ca 2+ ] i ). T2DM impaired cardiac function, disturbed glucose uptake, and damaged microvascular barrier, which were further aggravated by TRPV1 -/- Exposure to HG-HF, particularly in TRPV1 -/- CMECs, led to a higher level of apoptosis and a lower level of nitric oxide production in viable CMECs. HG-HF markedly enhanced generation of reactive oxygen species and nitrotyrosine, especially in the absence of TRPV1. H 2 O 2 administration reduced TRPV1 expression in CMECs. HG-HF significantly depressed expression of PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) and OPA1 (optic atrophy 1) by reducing [Ca 2+ ] i , whereas OPA1 supplementation partly reversed those detrimental effects induced by TRPV1 -/- Furthermore, capsaicin treatment not only attenuated CMECs injury induced by HG-HF but also mitigated cardiac microvascular injury induced by T2DM. Collectively, T2DM leads to cardiac microvascular injury by exacerbating the vicious circle of TRPV1 blockage and reactive oxygen species overload. Long-term capsaicin can protect cardiac microvessels against T2DM via suppressing oxidative/nitrative stress mediated by TRPV1/Ca 2+ /PGC-1α/OPA1 pathway in CMECs. © 2018 American Heart Association, Inc.

  14. Identification of polymer types and additives in marine microplastic particles using pyrolysis-GC/MS and scanning electron microscopy.

    PubMed

    Fries, Elke; Dekiff, Jens H; Willmeyer, Jana; Nuelle, Marie-Theres; Ebert, Martin; Remy, Dominique

    2013-10-01

    Any assessment of plastic contamination in the marine environment requires knowledge of the polymer type and the additive content of microplastics. Sequential pyrolysis-gas chromatography coupled to mass spectrometry (Pyr-GC/MS) was applied to simultaneously identify polymer types of microplastic particles and associated organic plastic additives (OPAs). In addition, a scanning electron microscope equipped with an energy-dispersive X-ray microanalyser was used to identify the inorganic plastic additives (IPAs) contained in these particles. A total of ten particles, which were optically identified as potentially being plastics, were extracted from two sediment samples collected from Norderney, a North Sea island, by density separation in sodium chloride. The weights of these blue, white and transparent fragments varied between 10 and 350 μg. Polymer types were identified by comparing the resulting pyrograms with those obtained from the pyrolysis of selected standard polymers. The particles consisted of polyethylene (PE), polypropylene, polystyrene, polyamide, chlorinated PE and chlorosulfonated PE. The polymers contained diethylhexyl phthalate, dibutyl phthalate, diethyl phthalate, diisobutyl phthalate, dimethyl phthalate, benzaldehyde and 2,4-di-tert-butylphenol. Sequential Py-GC/MS was found to be an appropriate tool for identifying marine microplastics for polymer types and OPAs. The IPAs identified were titanium dioxide nanoparticles (TiO2-NPs), barium, sulphur and zinc. When polymer-TiO2 composites are degraded in the marine environment, TiO2-NPs are probably released. Thus, marine microplastics may act as a TiO2-NP source, which has not yet been considered.

  15. Mitochondrial dysfunction-associated OPA1 cleavage contributes to muscle degeneration: preventative effect of hydroxytyrosol acetate.

    PubMed

    Wang, X; Li, H; Zheng, A; Yang, L; Liu, J; Chen, C; Tang, Y; Zou, X; Li, Y; Long, J; Liu, J; Zhang, Y; Feng, Z

    2014-11-13

    Mitochondrial dysfunction contributes to the development of muscle disorders, including muscle wasting, muscle atrophy and degeneration. Despite the knowledge that oxidative stress closely interacts with mitochondrial dysfunction, the detailed mechanisms remain obscure. In this study, tert-butylhydroperoxide (t-BHP) was used to induce oxidative stress on differentiated C2C12 myotubes. t-BHP induced significant mitochondrial dysfunction in a time-dependent manner, accompanied by decreased myosin heavy chain (MyHC) expression at both the mRNA and protein levels. Consistently, endogenous reactive oxygen species (ROS) overproduction triggered by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), a mitochondrial oxidative phosphorylation inhibitor, was accompanied by decreased membrane potential and decreased MyHC protein content. However, the free radical scavenger N-acetyl-L-cysteine (NAC) efficiently reduced the ROS level and restored MyHC content, suggesting a close association between ROS and MyHC expression. Meanwhile, we found that both t-BHP and FCCP promoted the cleavage of optic atrophy 1 (OPA1) from the long form into short form during the early stages. In addition, the ATPase family gene 3-like 2, a mitochondrial inner membrane protease, was also markedly increased. Moreover, OPA1 knockdown in myotubes was accompanied by decreased MyHC content, whereas NAC failed to prevent FCCP-induced MyHC decrease with OPA1 knockdown, suggesting that ROS might affect MyHC content by modulating OPA1 cleavage. In addition, hydroxytyrosol acetate (HT-AC), an important compound in virgin olive oil, could significantly prevent t-BHP-induced mitochondrial membrane potential and cell viability loss in myotubes. Specifically, HT-AC inhibited t-BHP-induced OPA1 cleavage and mitochondrial morphology changes, accompanied by improvement on mitochondrial oxygen consumption capacity, ATP productive potential and activities of mitochondrial complex I, II and V. Moreover, both t-BHP- and FCCP-induced MyHC decrease was sufficiently inhibited by HT-AC. Taken together, our data provide evidence indicating that mitochondrial dysfunction-associated OPA1 cleavage may contribute to muscle degeneration, and olive oil compounds could be effective nutrients for preventing the development of muscle disorders.

  16. Expression of Opacity Proteins Interferes with the Transmigration of Neisseria gonorrhoeae across Polarized Epithelial Cells.

    PubMed

    Stein, Daniel C; LeVan, Adriana; Hardy, Britney; Wang, Liang-Chun; Zimmerman, Lindsey; Song, Wenxia

    2015-01-01

    Neisseria gonorrhoeae (GC) establishes infection at the mucosal surface of the human genital tract, most of which is lined with polarized epithelial cells. GC can cause localized as well as disseminated infections, leading to various complications. GC constantly change their surface structures via phase and antigenic variation, which has been implicated as a means for GC to establish infection at various anatomic locations of male and female genital tracks. However, the exact contribution of each surface molecule to bacterial infectivity remains elusive due to their phase variation. Using a GC derivative that is genetically devoid of all opa genes (MS11∆Opa), this study shows that Opa expression interferes with GC transmigration across polarized human epithelial cells. MS11∆Opa transmigrates across polarized epithelial cells much faster and to a greater extent than MS11Opa+, while adhering at a similar level as MS11Opa+. When MS11Opa+, able to phase vary Opa expression, was inoculated, only those bacteria that turn off Opa expression transmigrate across the polarized epithelial monolayer. Similar to bacteria alone or co-cultured with non-polarized epithelial cells, MS11∆Opa fails to form large microcolonies at the apical surface of polarized epithelial cells. Apical inoculation of MS11Opa+, but not MS11∆Opa, induces the recruitment of the Opa host-cell receptor carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) to the apical junction and the vicinity of bacterial adherent sites. Our results suggest that Opa expression limits gonococcal ability to invade into subepithelial tissues by forming tight interactions with neighboring bacteria and by inducing CEACAM redistribution to cell junctions.

  17. Insulin stimulates mitochondrial fusion and function in cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 signaling pathway.

    PubMed

    Parra, Valentina; Verdejo, Hugo E; Iglewski, Myriam; Del Campo, Andrea; Troncoso, Rodrigo; Jones, Deborah; Zhu, Yi; Kuzmicic, Jovan; Pennanen, Christian; Lopez-Crisosto, Camila; Jaña, Fabián; Ferreira, Jorge; Noguera, Eduard; Chiong, Mario; Bernlohr, David A; Klip, Amira; Hill, Joseph A; Rothermel, Beverly A; Abel, Evan Dale; Zorzano, Antonio; Lavandero, Sergio

    2014-01-01

    Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machinery, is dramatically altered in obese and insulin-resistant patients. Given the role of insulin in the control of cardiac energetics, the goal of this study was to investigate whether insulin affects mitochondrial dynamics in cardiomyocytes. Confocal microscopy and the mitochondrial dye MitoTracker Green were used to obtain three-dimensional images of the mitochondrial network in cardiomyocytes and L6 skeletal muscle cells in culture. Three hours of insulin treatment increased Opa-1 protein levels, promoted mitochondrial fusion, increased mitochondrial membrane potential, and elevated both intracellular ATP levels and oxygen consumption in cardiomyocytes in vitro and in vivo. Consequently, the silencing of Opa-1 or Mfn2 prevented all the metabolic effects triggered by insulin. We also provide evidence indicating that insulin increases mitochondrial function in cardiomyocytes through the Akt-mTOR-NFκB signaling pathway. These data demonstrate for the first time in our knowledge that insulin acutely regulates mitochondrial metabolism in cardiomyocytes through a mechanism that depends on increased mitochondrial fusion, Opa-1, and the Akt-mTOR-NFκB pathway.

  18. Insulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 Signaling Pathway

    PubMed Central

    Parra, Valentina; Verdejo, Hugo E.; Iglewski, Myriam; del Campo, Andrea; Troncoso, Rodrigo; Jones, Deborah; Zhu, Yi; Kuzmicic, Jovan; Pennanen, Christian; Lopez‑Crisosto, Camila; Jaña, Fabián; Ferreira, Jorge; Noguera, Eduard; Chiong, Mario; Bernlohr, David A.; Klip, Amira; Hill, Joseph A.; Rothermel, Beverly A.; Abel, Evan Dale; Zorzano, Antonio; Lavandero, Sergio

    2014-01-01

    Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machinery, is dramatically altered in obese and insulin-resistant patients. Given the role of insulin in the control of cardiac energetics, the goal of this study was to investigate whether insulin affects mitochondrial dynamics in cardiomyocytes. Confocal microscopy and the mitochondrial dye MitoTracker Green were used to obtain three-dimensional images of the mitochondrial network in cardiomyocytes and L6 skeletal muscle cells in culture. Three hours of insulin treatment increased Opa-1 protein levels, promoted mitochondrial fusion, increased mitochondrial membrane potential, and elevated both intracellular ATP levels and oxygen consumption in cardiomyocytes in vitro and in vivo. Consequently, the silencing of Opa-1 or Mfn2 prevented all the metabolic effects triggered by insulin. We also provide evidence indicating that insulin increases mitochondrial function in cardiomyocytes through the Akt-mTOR-NFκB signaling pathway. These data demonstrate for the first time in our knowledge that insulin acutely regulates mitochondrial metabolism in cardiomyocytes through a mechanism that depends on increased mitochondrial fusion, Opa-1, and the Akt-mTOR-NFκB pathway. PMID:24009260

  19. A phosphine mediated sequential annulation process of 2-tosylaminochalcones with MBH carbonates to construct functionalized aza-benzobicyclo[4.3.0] derivatives.

    PubMed

    Zhang, Qinglong; Zhu, Yannan; Jin, Hongxing; Huang, You

    2017-04-04

    A novel phosphine mediated sequential annulation process to construct functionalized aza-benzobicyclo[4.3.0] derivatives has been developed involving a one-pot sequential catalytic and stoichiometric process, which generates a series of benzobicyclo[4.3.0] compounds containing one quaternary center with up to 94% yield and 20 : 1 dr value. In this reaction, MBH carbonates act as 1,2,3-C 3 synthons.

  20. Multiethnic involvement in autosomal-dominant optic atrophy in Singapore.

    PubMed

    Loo, J L; Singhal, S; Rukmini, A V; Tow, S; Amati-Bonneau, P; Procaccio, V; Bonneau, D; Gooley, J J; Reynier, P; Ferré, M; Milea, D

    2017-03-01

    PurposeAutosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore.Patients and methodsPreliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene.ResultsAmong 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA.ConclusionWe report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing 'ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia.

  1. Multiethnic involvement in autosomal-dominant optic atrophy in Singapore

    PubMed Central

    Loo, J L; Singhal, S; Rukmini, A V; Tow, S; Amati-Bonneau, P; Procaccio, V; Bonneau, D; Gooley, J J; Reynier, P; Ferré, M; Milea, D

    2017-01-01

    Purpose Autosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore. Patients and methods Preliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene. Results Among 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA. Conclusion We report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing ‘ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia. PMID:27858935

  2. Frictional Properties of Opalinus Clay: Implications for Nuclear Waste Storage

    NASA Astrophysics Data System (ADS)

    Orellana, L. F.; Scuderi, M. M.; Collettini, C.; Violay, M.

    2018-01-01

    The kaolinite-bearing Opalinus Clay (OPA) is the host rock proposed in Switzerland for disposal of radioactive waste. However, the presence of tectonic faults intersecting the OPA formation put the long-term safety performance of the underground repository into question due to the possibility of earthquakes triggered by fault instability. In this paper, we study the frictional properties of the OPA shale. To do that, we have carried out biaxial direct shear experiments under conditions typical of nuclear waste storage. We have performed velocity steps (1-300 μm/s) and slide-hold-slide tests (1-3,000 s) on simulated fault gouge at different normal stresses (4-30 MPa). To establish the deformation mechanisms, we have analyzed the microstructures of the sheared samples through scanning electron microscopy. Our results show that peak (μpeak) and steady state friction (μss) range from 0.21 to 0.52 and 0.14 to 0.39, respectively, thus suggesting that OPA fault gouges are weak. The velocity dependence of friction indicates a velocity strengthening regime, with the friction rate parameter (a - b) that decreases with normal stress. Finally, the zero healing values imply a lack of restrengthening during interseismic periods. Taken together, if OPA fault reactivates, our experimental evidence favors an aseismic slip behavior, making the nucleation of earthquakes difficult, and long-term weakness, resulting in stable fault creeping over geological times. Based on the results, our study confirms the seismic safety of the OPA formation for a nuclear waste repository.

  3. Line-of-sight measurements for the NIF Neutron Imaging System and determination of line-of-sight offsets in OPAS 90-135 images

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

    Frank, Matthias; Fittinghoff, David N.; Bower, Dan E.

    2011-05-13

    This report describes line-of-sight (LOS) measurements for the NIF Neutron Imaging System (NIS) and a characterization of the NIS LOS relative to OPAS 90-135 that were performed during the NIS commissioning Nov. 2010 – Jan. 2011. As described here, data from those measurements were used to determine the relative offsets between the TCC position (x and y pixel coordinates in OPAS images) and the NIS LOS as functions of the OPAS focal distance. This data is needed to place the NIS pinhole array (PHA) onto the NIS LOS with high precision using OPAS imaging of alignment fiducials attached to themore » front and the back of the PHA. (A description of the PHA alignment fiducials, data from metrology performed on the fiducials and a description on how these fiducials were used to align the PHA for the first NIS imaging shot on Feb,. 17, 2011 will be summarized in an upcoming separate report. This report consists of an overview given in this document and a main body that consists of a set of viewgraphs (see Appendix 1) that were iterated and refined within the NIS team and with the Alignment Working Group and that contain more detailed information, schematics and calculations of the NIS line of sight offset from the OPAS LOS. See also Drury, “OPAS 90-135 Registration of Neutron Imaging System Line of Sight,” January 2011, NIF-5035484.« less

  4. Evaluation of a contact lens-embedded sensor for intraocular pressure measurement.

    PubMed

    Twa, Michael D; Roberts, Cynthia J; Karol, Huikai J; Mahmoud, Ashraf M; Weber, Paul A; Small, Robert H

    2010-08-01

    To evaluate a novel contact lens-embedded pressure sensor for continuous measurement of intraocular pressure (IOP). Repeated measurements of IOP and ocular pulse amplitude (OPA) were recorded in 12 eyes of 12 subjects in sitting and supine positions using 3 configurations of the dynamic contour tonometer: slit-lamp mounted (DCT), hand-held (HH), and contact lens-embedded sensor (CL). The IOP and OPA for each condition were compared using repeated measures ANOVA and the 95% limits of agreement were calculated. The sitting IOP (mean and 95% CI) for each configuration was DCT: 16.3 mm Hg (15.6 to 17.1 mm Hg), HH: 16.6 mm Hg (15.6 to 17.6 mm Hg), and CL: 15.7 mm Hg (15 to 16.3 mm Hg). The sitting OPA for each configuration was DCT: 2.4 mm Hg (2.1 to 2.6 mm Hg), HH: 2.4 mm Hg (2.1 to 2.7 mm Hg), and CL: 2.1 mm Hg (1.8 to 2.3 mm Hg). Supine IOP and OPA measurements with the CL and HH sensors were both greater than their corresponding sitting measurements, but were significantly less with the CL sensor than the HH sensor. The mean difference and 95% Limits of Agreement were smallest for the DCT and CL sensor comparisons (0.7+/-3.9 mm Hg) and widest for the CL and HH sensors (-1.9+/-7.25 mm Hg); these wider limits were attributed to greater HH measurement variability. The CL sensor was comparable to HH and DCT sensors with sitting subjects and is a viable method for measuring IOP and OPA. Supine measurements of IOP and OPA were greater than sitting conditions and were comparatively lower with the CL sensor. HH measurements were more variable than CL measurements and this influenced the Limits of Agreement for both sitting and supine conditions.

  5. Mutation analysis of seven known glaucoma-associated genes in Chinese patients with glaucoma.

    PubMed

    Huang, Xiaobo; Li, Miaoling; Guo, Xiangming; Li, Shiqiang; Xiao, Xueshan; Jia, Xiaoyun; Liu, Xing; Zhang, Qingjiong

    2014-05-13

    To evaluate mutations in the MYOC, WDR36, OPTN, OPA1, NTF4, CYP1B1, and LTBP2 genes in a cohort of Chinese patients with primary glaucoma. Genomic DNA was prepared from 683 unrelated patients, including 50 with primary congenital glaucoma, 104 with juvenile open-angle glaucoma (JOAG), 186 with primary open-angle glaucoma (POAG), and 343 with primary angle-closure glaucoma (PACG). Mutations in the seven genes in 257 patients (36 with JOAG, 89 with POAG, and 132 with PACG) were initially analyzed by exome sequencing and then confirmed by Sanger sequencing. In addition, Sanger sequencing was used to detect MYOC mutations in the remaining 426 patients. Exome sequencing identified 19 mutations (6 in MYOC, 9 in WDR36, 3 in OPA1, and 1 in OPTN) in 20 of 257 patients, including 4 patients with JOAG, 8 patients with POAG, and 8 patients with PACG. No mutation was detected in the other three genes. In addition, Sanger sequencing detected additional MYOC mutations in 5 of the remaining 426 patients, including 3 patients with JOAG and 2 patients with POAG. Twenty-two mutations in MYOC, WDR36, OPA1, and OPTN were detected in 25 of the 683 patients with primary glaucoma, including nine MYOC mutations in 11 patients, nine WDR36 mutations in 11 patients, three OPA1 mutations in 3 patients, and one OPTN mutation in a patient who also carried a MYOC mutation. Eight mutations in MYOC, WDR36, and OPA1 in 8 of the 343 PACG patients are of uncertain significance and need to be analyzed further. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  6. Effect of quantifying peptide release on ruminal protein degradation determined using the inhibitor in vitro system

    USDA-ARS?s Scientific Manuscript database

    The aim of this work was to compare use of an o-phthaldialdehyde (OPA) colorimetric assay (OPA-C), which responds to both free AA and peptides, with an OPA fluorimetric assay (OPA-F), which is insensitive to peptides, to quantify rates of ruminal protein degradation in the inhibitor in vitro system ...

  7. LSGermOPA, a custom OPA of 384 EST-derived SNPs for high-throughput lettuce (Lactuca sativa L.) germplasm fingerprinting

    USDA-ARS?s Scientific Manuscript database

    We assessed the genetic diversity and population structure among 148 cultivated lettuce (Lactuca sativa L.) accessions using the high-throughput GoldenGate assay and 384 EST (Expressed Sequence Tag)-derived SNP (single nucleotide polymorphism) markers. A custom OPA (Oligo Pool All), LSGermOPA was fo...

  8. Milestone-compatible neurology resident assessments: A role for observable practice activities.

    PubMed

    Jones, Lyell K; Dimberg, Elliot L; Boes, Christopher J; Eggers, Scott D Z; Dodick, David W; Cutsforth-Gregory, Jeremy K; Leep Hunderfund, Andrea N; Capobianco, David J

    2015-06-02

    Beginning in 2014, US neurology residency programs were required to report each trainee's educational progression within 29 neurology Milestone competency domains. Trainee assessment systems will need to be adapted to inform these requirements. The primary aims of this study were to validate neurology resident assessment content using observable practice activities (OPAs) and to develop assessment formats easily translated to the Neurology Milestones. A modified Delphi technique was used to establish consensus perceptions of importance of 73 neurology OPAs among neurology educators and trainees at 3 neurology residency programs. A content validity score (CVS) was derived for each neurology OPA, with scores ≥4.0 determined in advance to indicate sufficient content validity. The mean CVS for all OPAs was 4.4 (range 3.5-5.0). Fifty-seven (78%) OPAs had a CVS ≥4.0, leaving 16 (22%) below the pre-established threshold for content validity. Trainees assigned a higher importance to individual OPAs (mean CVS 4.6) compared to faculty (mean 4.4, p = 0.016), but the effect size was small (η(2) = 0.10). There was no demonstrated effect of length of education experience on perceived importance of neurology OPAs (p = 0.23). Two sample resident assessment formats were developed, one using neurology OPAs alone and another using a combination of neurology OPAs and the Neurology Milestones. This study provides neurology training programs with content validity evidence for items to include in resident assessments, and sample assessment formats that directly translate to the Neurology Milestones. Length of education experience has little effect on perceptions of neurology OPA importance. © 2015 American Academy of Neurology.

  9. A Role for 2-Methyl Pyrrole in the Browning of 4-Oxopentanal and Limonene Secondary Organic Aerosol

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

    Aiona, Paige K.; Lee, Hyun Ji; Lin, Peng

    “Brown Carbon” (BrC) is a type of organic particulate matter that absorbs visible and near ultraviolet radiation. Reactions of carbonyls in secondary organic aerosol (SOA) produced from limonene with ammonia (NH3) or ammonium sulfate (AS) are known to produce BrC with a distinctive absorption band at 500 nm. Although the general mechanism for this process has been proposed in previous studies, the specific molecular structures of the light-absorbing species remain unclear. This study examined the browning processes occurring in aqueous solutions of AS and 4-oxopentanal (4-OPA), which has a 1,4-dicarbonyl structural motif present in many limonene SOA compounds. The reactionmore » of 4-OPA with AS in a bulk aqueous solution produces a 2-methyl pyrrole (2-MP) intermediate, which is not a strong light absorber by itself, but can react further with carbonyl compounds leading to the eventual formation of BrC chromophores. The direct involvement of 2-MP in the browning process was demonstrated by reacting 2-MP with 4-OPA and with limonene SOA, both of which produced BrC chromophores with distinctive absorption bands at visible wavelengths. The formation of BrC in reaction of 4-OPA with AS and ammonium nitrate (AN) was found to be accelerated by evaporation of the solution suggesting an important role of the dehydration processes in BrC formation from 1,4- dicarbonyls. 4-OPA was also found to produce BrC in aqueous reactions with a broad spectrum of amino acids and amines. The results suggest that 4-OPA may be the smallest atmospherically relevant compound capable of browning by the same mechanism as limonene SOA.« less

  10. Deregulation of Mitochondria-Shaping Proteins Opa-1 and Drp-1 in Manganese-Induced Apoptosis

    PubMed Central

    Alaimo, Agustina; Gorojod, Roxana M.; Beauquis, Juan; Muñoz, Manuel J.; Saravia, Flavia; Kotler, Mónica L.

    2014-01-01

    Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may provide new therapeutic tools for the treatment of Manganism and other neurodegenerative diseases. PMID:24632637

  11. Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis.

    PubMed

    Alaimo, Agustina; Gorojod, Roxana M; Beauquis, Juan; Muñoz, Manuel J; Saravia, Flavia; Kotler, Mónica L

    2014-01-01

    Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may provide new therapeutic tools for the treatment of Manganism and other neurodegenerative diseases.

  12. Syndromic parkinsonism and dementia associated with OPA 1 missense mutations

    PubMed Central

    Musumeci, Olimpia; Caporali, Leonardo; Zanna, Claudia; La Morgia, Chiara; Del Dotto, Valentina; Porcelli, Anna Maria; Rugolo, Michela; Valentino, Maria Lucia; Iommarini, Luisa; Maresca, Alessandra; Barboni, Piero; Carbonelli, Michele; Trombetta, Costantino; Valente, Enza Maria; Patergnani, Simone; Giorgi, Carlotta; Pinton, Paolo; Rizzo, Giovanni; Tonon, Caterina; Lodi, Raffaele; Avoni, Patrizia; Liguori, Rocco; Baruzzi, Agostino; Toscano, Antonio; Zeviani, Massimo

    2015-01-01

    Objective Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. Here, we report 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia. Methods Patients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, and underwent muscle and brain magnetic resonance spectroscopy (MRS), and muscle biopsy and fibroblasts were analyzed. Candidate genes were sequenced, and mtDNA was analyzed for rearrangements. Results Affected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism, and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed cytochrome c oxidase‐negative fibers and mtDNA multiple deletions, and MRS displayed defective oxidative metabolism in muscle and brain. We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. Fibroblast studies showed a reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy. Interpretation The association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism. Ann Neurol 2015;78:21–38 PMID:25820230

  13. Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1

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

    Kieper, Nicole; Holmstroem, Kira M.; Ciceri, Dalila

    2010-04-15

    Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and Drosophila S2R+ cells, we found elongatedmore » mitochondria by live cell imaging. Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. Finally, co-immunoprecipitation showed direct interaction of Omi/HtrA2 with endogenous OPA1. Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders.« less

  14. Mechanistic perspective of mitochondrial fusion: tubulation vs. fragmentation.

    PubMed

    Escobar-Henriques, Mafalda; Anton, Fabian

    2013-01-01

    Mitochondrial fusion is a fundamental process driven by dynamin related GTPase proteins (DRPs), in contrast to the general SNARE-dependence of most cellular fusion events. The DRPs Mfn1/Mfn2/Fzo1 and OPA1/Mgm1 are the key effectors for fusion of the mitochondrial outer and inner membranes, respectively. In order to promote fusion, these two DRPs require post-translational modifications and proteolysis. OPA1/Mgm1 undergoes partial proteolytic processing, which results in a combination between short and long isoforms. In turn, ubiquitylation of mitofusins, after oligomerization and GTP hydrolysis, promotes and positively regulates mitochondrial fusion. In contrast, under conditions of mitochondrial dysfunction, negative regulation by proteolysis on these DRPs results in mitochondrial fragmentation. This occurs by complete processing of OPA1 and via ubiquitylation and degradation of mitofusins. Mitochondrial fragmentation contributes to the elimination of damaged mitochondria by mitophagy, and may play a protective role against Parkinson's disease. Moreover, a link of Mfn2 to Alzheimer's disease is emerging and mutations in Mfn2 or OPA1 cause Charcot-Marie-Tooth type 2A neuropathy or autosomal-dominant optic atrophy. Here, we summarize our current understanding on the molecular mechanisms promoting or inhibiting fusion of mitochondrial membranes, which is essential for cellular survival and disease control. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Hereditary motor and sensory neuropathy type VI with optic atrophy.

    PubMed

    Voo, Irene; Allf, Bryan E; Udar, Nitin; Silva-Garcia, Rosamaria; Vance, Jeffrey; Small, Kent W

    2003-10-01

    To present the detailed clinical findings of a large family with hereditary motor and sensory neuropathy type VI (HMSN VI), a syndrome featuring optic atrophy. Observational case series. A detailed history was obtained and physical examination was made of the extended family of the proband for evidence of neurologic dysfunction. The OPA1 gene was screened for mutations by direct DNA sequencing. Twelve of 97 family members examined are affected with signs of HMSN VI. Three other members have either optic atrophy or peripheral neuropathy, thus allowing an appreciation of the full clinical spectrum of disease. No mutations were found in the OPA1 gene. This family demonstrates the variable expressivity of this disorder as well as incomplete penetrance. This is the largest known family with HMSN VI. No association was found with changes in the OPA1 gene.

  16. The occipital place area represents the local elements of scenes

    PubMed Central

    Kamps, Frederik S.; Julian, Joshua B.; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D.

    2016-01-01

    Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents in not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements – both in spatial boundary and scene content representation – while PPA and RSC represent global scene properties. PMID:26931815

  17. The occipital place area represents the local elements of scenes.

    PubMed

    Kamps, Frederik S; Julian, Joshua B; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D

    2016-05-15

    Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents is not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found that OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements - both in spatial boundary and scene content representation - while PPA and RSC represent global scene properties. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division

    PubMed Central

    Cho, Bongki; Cho, Hyo Min; Jo, Youhwa; Kim, Hee Dae; Song, Myungjae; Moon, Cheil; Kim, Hyongbum; Kim, Kyungjin; Sesaki, Hiromi; Rhyu, Im Joo; Kim, Hyun; Sun, Woong

    2017-01-01

    Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated. Here we report spontaneous and repetitive constriction of mitochondrial inner compartment (CoMIC) associated with subsequent division in neurons. Although CoMIC is potentiated by inhibition of Drp1 and occurs at the potential division spots contacting the endoplasmic reticulum, it appears on IMM independently of OMM. Intra-mitochondrial influx of Ca2+ induces and potentiates CoMIC, and leads to K+-mediated mitochondrial bulging and depolarization. Synergistically, optic atrophy 1 (Opa1) also regulates CoMIC via controlling Mic60-mediated OMM–IMM tethering. Therefore, we propose that CoMIC is a priming event for efficient mitochondrial division. PMID:28598422

  19. Pathology of ovine pulmonary adenocarcinoma.

    PubMed

    De las Heras, M; González, L; Sharp, J M

    2003-01-01

    Clinical, gross pathology, histopathology and electron microscopy of the ovine pulmonary adenocarcinoma (OPA, jaagsiekte) either natural or experimentally induced in sheep, goat and moufflon are described. OPA is caused by an oncogenic betaretrovirus,jaagsiekte sheep retrovirus (JSRV). Most natural cases of OPA appear in animals 1-4 years old. There is no evidence of sex or breed susceptibility. Sheep affected by OPA show an afebrile respiratory illness associated with loss of weight. A very characteristic clinical sign is moist rales caused by the accumulation of fluid in the respiratory airways which is discharged from the nostrils when the head is lowered. Gross lesions are confined to the lungs but occasionally thoracic or extrathoracic structures are also affected. Two pathologic forms of OPA are currently recognized, classical and atypical. In classical forms the neoplastic lesions occurs particularly in the cranioventral parts of all lung lobes. They are diffuse or nodular, light grey or light purple in colour. On the cut surface the tumour is moist, and frothy fluid may pour from the airways on slight pressure. Atypical forms tend to be more nodular in both early and advanced tumours. They are pearly white in colour, very hard in consistency, very well demarcated from the surrounding parenchyma and their surface is dry. Histology of the lung sections reveals the presence of several foci of epithelial cell neoplastic proliferation in both alveolar or bronchiolar regions. The tumours, derived from type II pneumocytes and Clara cells, proliferate into mostly papillary but also acinar or occasionally solid growths. The tumour generally shows a benign histological pattern but intra- and extrathoracic metastases have been detected in some cases. Several considerations suggest that the tumour should be classified as an adenocarcinoma of the lung. The histology of atypical OPA is similar to that of the classical disease, with an increase in the stromal reaction accompanying the epithelial proliferations. Pathological features of OPA induced experimentally in sheep, or of OPA in goats and moufflon are similar to those described in sheep. Detailed electron microscopy of tumour material confirms that type II pneumocytes and Clara bronchiolar epithelial cells are the origin of the neoplasia. Also included in this chapter is a description of the morphology of the viral particles associated with OPA.

  20. Effects of a combined parent-student alcohol prevention program on intermediate factors and adolescents' drinking behavior: A sequential mediation model.

    PubMed

    Koning, Ina M; Maric, Marija; MacKinnon, David; Vollebergh, Wilma A M

    2015-08-01

    Previous work revealed that the combined parent-student alcohol prevention program (PAS) effectively postponed alcohol initiation through its hypothesized intermediate factors: increase in strict parental rule setting and adolescents' self-control (Koning, van den Eijnden, Verdurmen, Engels, & Vollebergh, 2011). This study examines whether the parental strictness precedes an increase in adolescents' self-control by testing a sequential mediation model. A cluster randomized trial including 3,245 Dutch early adolescents (M age = 12.68, SD = 0.50) and their parents randomized over 4 conditions: (1) parent intervention, (2) student intervention, (3) combined intervention, and (4) control group. Outcome measure was amount of weekly drinking measured at age 12 to 15; baseline assessment (T0) and 3 follow-up assessments (T1-T3). Main effects of the combined and parent intervention on weekly drinking at T3 were found. The effect of the combined intervention on weekly drinking (T3) was mediated via an increase in strict rule setting (T1) and adolescents' subsequent self-control (T2). In addition, the indirect effect of the combined intervention via rule setting (T1) was significant. No reciprocal sequential mediation (self-control at T1 prior to rules at T2) was found. The current study is 1 of the few studies reporting sequential mediation effects of youth intervention outcomes. It underscores the need of involving parents in youth alcohol prevention programs, and the need to target both parents and adolescents, so that change in parents' behavior enables change in their offspring. (c) 2015 APA, all rights reserved).

  1. Differences between work and leisure in temporal patterns of objectively measured physical activity among blue-collar workers.

    PubMed

    Hallman, David M; Mathiassen, Svend Erik; Gupta, Nidhi; Korshøj, Mette; Holtermann, Andreas

    2015-09-28

    Leisure time physical activity (LTPA) is generally associated with favorable cardiovascular health outcomes, while occupational physical activity (OPA) shows less clear, or even opposite, cardiovascular effects. This apparent paradox is not sufficiently understood, but differences in temporal patterns of OPA and LTPA have been suggested as one explanation. Our aim was to investigate the extent to which work and leisure (non-occupational time) differ in temporal activity patterns among blue-collar workers, and to assess the modification of these patterns by age and gender. This study was conducted on a cross-sectional sample of male (n = 108) and female (n = 83) blue-collar workers, aged between 21 and 65 years. Physical activity and sedentary behavior were assessed using accelerometers (Actigraph GT3X+) worn on the thigh and trunk for four consecutive days. Temporal patterns of OPA and LTPA were retrieved using Exposure Variation Analysis (EVA), and expressed in terms of percentage of work and leisure time spent in uninterrupted periods of different durations (<1 min, 1-5 min, 5-10 min, 10-30 min, 30-60 min and > 60 min) of sitting, standing, and walking. Repeated measures ANOVA and linear regression analyses were used to test a) possible differences between OPA and LTPA in selected EVA derivatives, and b) the modification of these differences by age and gender. OPA showed a larger percentage time walking in brief (<5 min) periods [mean (SD): 33.4 % (12.2)], and less time in prolonged (>30 min) sitting [7.0 % (9.3)] than LTPA [walking 15.4 % (5.0); sitting 31.9 % (15.3)], even after adjustment for the difference between work and leisure in total time spent in each activity type. These marked differences in the temporal pattern of OPA and LTPA were modified by gender, but not age. We found that the temporal patterns of OPA and LTPA among blue-collar workers were markedly different even after adjustment for total physical activity time, and that this difference was modified by gender. We recommend using EVA derivatives in future studies striving to disentangle the apparent paradoxical cardiovascular effect of physical activity at work and during leisure.

  2. Telephone Follow-Up following Office Anorectal Surgery

    PubMed Central

    Fallaize, Rebecca C; Tinline-Purvis, Christine; Dixon, Anthony R; Pullyblank, Anne-Marie

    2008-01-01

    INTRODUCTION Patients with minor anorectal conditions are frequently reviewed at an 8-week out-patient appointment (OPA). This study was designed to assess whether telephone follow-up could reduce OPA numbers whilst maintaining patient satisfaction. PATIENTS AND METHODS Over an 11-month period, 46 patients (23 male) underwent banding of haemorrhoids and 14 were prescribed medical treatment for fissure-in-ano (3 male). All were telephoned at 6 weeks and were offered an 8-week OPA if they had continuing problems. Patients were telephoned at a later date by a member of the hospital's patient panel to assess satisfaction. RESULTS Overall, 88% were contacted at 6 weeks, 60% at the first attempt; 40% required two or more attempts. Of those who underwent banding, 68% were asymptomatic, 17% requested an OPA for re-banding and 15% requested an OPA for a different problem. Of fissure patients, 25% were cured; the remainder were prescribed either second-line medical treatment (8%), anorectal physiology (42%) or surgery (25%). All avoided an OPA. Of a potential 60 OPAs, 47 were saved by telephone follow-up. None of 7 non-contactable patients accepted a written offer of an OPA. Overall, 89% of patients were contacted by the patient panel; of these patients, 93% reported a high level of satisfaction. CONCLUSIONS Telephone follow-up can reduce the number of OPAs following out-patient treatment of minor anorectal conditions whilst maintaining a high level of patient satisfaction. However, it requires considerable consultant time. This process could be developed into either a nurse-led service with booked telephone appointments or a patient-led service to a dedicated hotline. PMID:18598594

  3. Telephone follow-up following office anorectal surgery.

    PubMed

    Fallaize, Rebecca C; Tinline-Purvis, Christine; Dixon, Anthony R; Pullyblank, Anne-Marie

    2008-09-01

    Patients with minor anorectal conditions are frequently reviewed at an 8-week out-patient appointment (OPA). This study was designed to assess whether telephone follow-up could reduce OPA numbers whilst maintaining patient satisfaction. Over an 11-month period, 46 patients (23 male) underwent banding of haemorrhoids and 14 were prescribed medical treatment for fissure-in-ano (3 male). All were telephoned at 6 weeks and were offered an 8-week OPA if they had continuing problems. Patients were telephoned at a later date by a member of the hospital's patient panel to assess satisfaction. Overall, 88% were contacted at 6 weeks, 60% at the first attempt; 40% required two or more attempts. Of those who underwent banding, 68% were asymptomatic, 17% requested an OPA for re-banding and 15% requested an OPA for a different problem. Of fissure patients, 25% were cured; the remainder were prescribed either second-line medical treatment (8%), anorectal physiology (42%) or surgery (25%). All avoided an OPA. Of a potential 60 OPAs, 47 were saved by telephone follow-up. None of 7 non-contactable patients accepted a written offer of an OPA. Overall, 89% of patients were contacted by the patient panel; of these patients, 93% reported a high level of satisfaction. Telephone follow-up can reduce the number of OPAs following out-patient treatment of minor anorectal conditions whilst maintaining a high level of patient satisfaction. However, it requires considerable consultant time. This process could be developed into either a nurse-led service with booked telephone appointments or a patient-led service to a dedicated hotline.

  4. Mycobacterium massiliense BRA100 strain recovered from postsurgical infections: resistance to high concentrations of glutaraldehyde and alternative solutions for high level disinfection.

    PubMed

    Lorena, Nádia Suely de Oliveira; Pitombo, Marcos Bettini; Côrtes, Patrícia Barbur; Maya, Maria Cristina Araújo; Silva, Marlei Gomes da; Carvalho, Ana Carolina da Silva; Coelho, Fábrice Santana; Miyazaki, Neide Hiromi Tokumaru; Marques, Elizabeth Andrade; Chebabo, Alberto; Freitas, Andréa D'Avila; Lupi, Otília; Duarte, Rafael Silva

    2010-10-01

    To evaluate the minimum inhibitory concentration (MIC) of GTA against these microorganisms and alternative disinfectants for high-level disinfection (HLD). Reference mycobacteria and clinical M. massiliense strains were included in this study. Active cultures were submitted to susceptibility qualitative tests with GTA dilutions (ranging from 1.5% to 8%), and commercial orthophthaldehyde (OPA) and peracetic acid (PA)-based solutions, during the period of exposure as recommended by National Agency of Sanitary Surveillance for HLD. All reference and M. massiliense non-BRA100 strains, recovered from sputum, were susceptible to any GTA concentration, OPA and PA solutions. M. massiliense BRA100 strains presented MIC of 8% GTA and were susceptible to OPA and PA. M. massiliense BRA100 strain is resistant to high GTA concentrations (up to 7%), which proves that this product is non-effective against specific rapidly growing mycobacteria and should be substituted by OPA or PA-based solutions for HLD.

  5. 140 W peak power laser system tunable in the LWIR.

    PubMed

    Gutty, François; Grisard, Arnaud; Larat, Christian; Papillon, Dominique; Schwarz, Muriel; Gerard, Bruno; Ostendorf, Ralf; Rattunde, Marcel; Wagner, Joachim; Lallier, Eric

    2017-08-07

    We present a high peak power rapidly tunable laser system in the long-wave infrared comprising an external-cavity quantum cascade laser (EC-QCL) broadly tunable from 8 to 10 µm and an optical parametric amplifier (OPA) based on quasi phase-matching in orientation-patterned gallium arsenide (OP-GaAs) of fixed grating period. The nonlinear crystal is pumped by a pulsed fiber laser system to achieve efficient amplification in the OPA. Quasi phase-matching remains satisfied when the EC-QCL wavelength is swept from 8 to 10 µm with a crystal of fixed grating period through tuning the pump laser source around 2 µm. The OPA demonstrates parametric amplification from 8 µm to 10 µm and achieves output peak powers up to 140 W with spectral linewidths below 3.5 cm -1 . The beam profile quality (M 2 ) remains below 3.4 in both horizontal and vertical directions. Compared to the EC-QCL, the linewidth broadening is attributed to a coupling with the OPA.

  6. Occupational and leisure-time physical activity and workload among construction workers – a randomized control study

    PubMed Central

    Karstad, K.; Søgaard, K.

    2016-01-01

    Background There is a lack of quantification of occupational physical activity (OPA) and leisure time physical activity (LTPA) among construction workers. Objectives To describe physical activity energy expenditure (PAEE), physical workload, and the effect of a PA-intervention among construction workers. Methods Sixty-seven Construction workers self-reported their physical activity (PA), had PA assessed directly (PAEE), and observed OPA using the tool “Posture, Activity, Tools and Handling.” The PA-intervention (Intervention; n = 29, Controls; n = 24) included 3x20-min training/week for 12 weeks. Results Baseline median OPA was 5036 MET-min/week and LTPA 2842 MET-min/week, p < 0.01. OPA directly recorded was (mean ± SE): 56.6 ± 3.2 J/kg/min and LTPA was: 35.7 ± 2.2 J/kg/min (p < 0.001). Manual material handling was performed for ≥ 25% of working time by more than 50% of the participants. Post-intervention, the training group reduced overall PAEE compared to the control group but not specifically during work. Conclusions OPA was within the maximum recommended level of 1/3 proposed in consensus guidelines but did not decrease with PA-intervention. PMID:27097799

  7. Pneumococcal vaccination in patients with systemic lupus erythematosus: A multicenter placebo-controlled randomized double-blind study.

    PubMed

    Grabar, Sophie; Groh, Matthieu; Bahuaud, Mathilde; Le Guern, Véronique; Costedoat-Chalumeau, Nathalie; Mathian, Alexis; Hanslik, Thomas; Guillevin, Loïc; Batteux, Frédéric; Launay, Odile

    2017-09-05

    Invasive pneumococcal disease and respiratory tract infections are both frequent and severe in patients with systemic lupus erythematosus (SLE). This study aimed to compare the immunological efficacy and safety of pneumococcal vaccination with the 23-valent polysaccharide (PPS) vaccine alone to a sequential immunization with the 7-valent pneumococcal conjugate (PnCj) vaccine followed by PPS in patients with SLE and stable diseaase. Multicenter randomized placebo-controlled double-blind trial: PPS vaccine alone (placebo-PPS group) or PnCj vaccine followed by PPS vaccine (PnCj-PPS group) 24weeks later. The primary endpoint was the rate of responders at week 28 to at least 5 of the 7 serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) shared by both PPS and PnCj. Pneumococcal IgG antibodies' opsonophagocytic activity (OPA) were also assessed. Twenty-five patients in the placebo-PPS group and 17 in the PnCj-PPS group were included in a modified intention-to-treat analysis. The primary endpoint was reached in 72% (18/25) in the placebo-PPS and 76% (13/17) in the PnCj-PPS group (p=0.75). There was no difference in the rates of responders with OPA. At week 52, 13/18 (72%) patients in the placebo-PPS group and 10/13 (77%) patients in the PnCj-PPS group (p=0.77) that met the primary endpoint at week 28 were still responders to ≥5/7 serotypes shared by both PPS and PnCj vaccines. Nine SLE flares were reported in 6 patients (4 in the placebo-PPS and 2 in the PnCj-PPS groups respectively, p=0.70). Sequential administration of PnCj vaccine followed by PPS vaccine is safe and shows short-term immunological efficacy in patients with SLE but was not superior to the PPS vaccine alone. www.clinicaltrials.gov, NCT NCT00611663. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Comparison of the efficacy of disinfectants in automated endoscope reprocessors for colonoscopes: tertiary amine compound (Sencron2®) versus ortho-phthalaldehyde (Cidex®OPA)

    PubMed Central

    Seo, Hyun Il; Lee, Dae Sung; Yoon, Eun Mi; Kwon, Min-Jung; Park, Hyosoon; Jung, Yoon Suk; Park, Jung Ho; Sohn, Chong Il

    2016-01-01

    Background/Aims To prevent the transmission of pathogens by endoscopes, following established reprocessing guidelines is critical. An ideal reprocessing step is simple, fast, and inexpensive. Here, we evaluated and compared the efficacy and safety of two disinfectants, a tertiary amine compound (TAC) and ortho-phthalaldehyde (OPA). Methods A total of 100 colonoscopes were randomly reprocessed using two same automated endoscope reprocessors, according to disinfectant. The exposure time was 10 minutes for 0.55% OPA (Cidex® OPA, Johnson & Johnson) and 5 minutes for 4% TAC (Sencron2®, Bab Gencel Pharma & Chemical Ind. Co.). Three culture samples were obtained from each colonoscope after reprocessing. Results A total of nine samples were positive among the 300 culture samples. The positive culture rate was not statistically different between the two groups (4% for OPA and 2% for TAC, P=0.501). There were no incidents related to safety during the study period. Conclusions TAC was non-inferior in terms of reprocessing efficacy to OPA and was safe to use. Therefore, TAC seems to be a good alternative disinfectant with a relatively short exposure time and is also less expensive than OPA. PMID:27175119

  9. Occupational Physical Activity, Overweight, and Mortality: A Follow-Up Study of 47,405 Norwegian Women and Men

    ERIC Educational Resources Information Center

    Graff-Iversen, Sidsel; Selmer, Randi; Sorensen, Marit; Skurtveit, Svetlana

    2007-01-01

    This population-based 24-year follow-up study evaluated the association of occupational physical activity (OPA) with overweight and mortality in 47,405 men and women, healthy at baseline, and reporting OPA as sedentary (reference), light, moderately heavy, or heavy. The adjusted odds ratio for overweight was slightly less than 1 for all categories…

  10. Effects of leisure-time and occupational physical activity on total mortality risk in NHANES III according to sex, ethnicity, central obesity, and age.

    PubMed

    Richard, Aline; Martin, Brian; Wanner, Miriam; Eichholzer, Monika; Rohrmann, Sabine

    2015-02-01

    Associations of physical activity with all-cause mortality seem to be quite strong, but little is known about potential effect modifiers as sex, race/ethnicity, age, and obesity. Data of the Third National Health and Nutrition Examination Survey (NHANES III), conducted 1988-1994 with mortality follow-up until 2006, were used to compare mortality risk between different levels of leisure-time physical activity (LTPA) and occupational physical activity (OPA). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). LTPA (n = 15,307) was inversely associated with all-cause mortality (HR 0.75, 95% CI 0.64-0.88 for regular vs. no LTPA). There was a statistically significant interaction with age (P = .03), with participants over 60 years of age benefitting more from regular or irregular LTPA. OPA was positively associated with all-cause mortality (HR 1.25, 95% CI 0.85-1.84 for high vs. low OPA), particularly among Mexican-Americans (HR 2.28, 95% CI 1.23-4.22); statistically significant interactions were observed for obesity and gender. LTPA clearly predicts all-cause mortality. However, associations between OPA and all-cause mortality are unclear and need further research with special regard to ethnic differences.

  11. Sequential mediating effects of provided and received social support on trait emotional intelligence and subjective happiness: A longitudinal examination in Hong Kong Chinese university students.

    PubMed

    Ye, Jiawen; Yeung, Dannii Y; Liu, Elaine S C; Rochelle, Tina L

    2018-04-03

    Past research has often focused on the effects of emotional intelligence and received social support on subjective well-being yet paid limited attention to the effects of provided social support. This study adopted a longitudinal design to examine the sequential mediating effects of provided and received social support on the relationship between trait emotional intelligence and subjective happiness. A total of 214 Hong Kong Chinese undergraduates were asked to complete two assessments with a 6-month interval in between. The results of the sequential mediation analysis indicated that the trait emotional intelligence measured in Time 1 indirectly influenced the level of subjective happiness in Time 2 through a sequential pathway of social support provided for others in Time 1 and social support received from others in Time 2. These findings highlight the importance of trait emotional intelligence and the reciprocal exchanges of social support in the subjective well-being of university students. © 2018 International Union of Psychological Science.

  12. Analysis of amino acid composition in proteins of animal tissues and foods as pre-column o-phthaldialdehyde derivatives by HPLC with fluorescence detection.

    PubMed

    Dai, Zhaolai; Wu, Zhenlong; Jia, Sichao; Wu, Guoyao

    2014-08-01

    Studies of protein nutrition and biochemistry require reliable methods for analysis of amino acid (AA) composition in polypeptides of animal tissues and foods. Proteins are hydrolyzed by 6M HCl (110°C for 24h), 4.2M NaOH (105°C for 20 h), or proteases. Analytical techniques that require high-performance liquid chromatography (HPLC) include pre-column derivatization with 4-chloro-7-nitrobenzofurazan, 9-fluorenyl methylchloroformate, phenylisothiocyanate, naphthalene-2,3-dicarboxaldehyde, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, and o-phthaldialdehyde (OPA). OPA reacts with primary AA (except cysteine or cystine) in the presence of 2-mercaptoethanol or 3-mercaptopropionic acid to form a highly fluorescent adduct. OPA also reacts with 4-amino-1-butanol and 4-aminobutane-1,3-diol produced from oxidation of proline and 4-hydroxyproline, respectively, in the presence of chloramine-T plus sodium borohydride at 60°C, or with S-carboxymethyl-cysteine formed from cysteine and iodoacetic acid at 25°C. Fluorescence of OPA derivatives is monitored at excitation and emission wavelengths of 340 and 455 nm, respectively. Detection limits are 50 fmol for AA. This technique offers the following advantages: simple procedures for preparation of samples, reagents, and mobile-phase solutions; rapid pre-column formation of OPA-AA derivatives and their efficient separation at room temperature (e.g., 20-25°C); high sensitivity of detection; easy automation on the HPLC apparatus; few interfering side reactions; a stable chromatography baseline for accurate integration of peak areas; and rapid regeneration of guard and analytical columns. Thus, the OPA method provides a useful tool to determine AA composition in proteins of animal tissues (e.g., skeletal muscle, liver, intestine, placenta, brain, and body homogenates) and foods (e.g., milk, corn grain, meat, and soybean meal). Copyright © 2014 Elsevier B.V. All rights reserved.

  13. 77 FR 55861 - Notice of Lodging of Consent Decree Under the Oil Pollution Act of 1990 (“OPA”)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-11

    ... DEPARTMENT OF JUSTICE Notice of Lodging of Consent Decree Under the Oil Pollution Act of 1990 (``OPA'') Notice is hereby given that on September 4, 2012, a proposed Consent Decree in United States et... International under Section 1002 of OPA and Section 48-1-90 of the South Carolina Pollution Control Act, S.C...

  14. Ground Demonstration of Planetary Gas Lidar Based on Optical Parametric Amplifier

    NASA Technical Reports Server (NTRS)

    Numata, Kenji; Riris, Haris; Li, Steve; Wu, Stewart; Kawa, Stephen R.; Krainak, Michael; Abshire, James

    2012-01-01

    We report on the development effort of a nanosecond-pulsed optical parametric amplifier (OPA) for remote trace gas measurements for Mars and Earth. The OPA output has high spectral purity and is widely tunable both at near-infrared and mid-infrared wavelengths, with an optical-optica1 conversion efficiency of up to approx 39 %. Using this laser source, we demonstrated open-path measurements of CH4 (3291 nm and 1651 nm), CO2 (1573 nm), H2O (1652 nm), and CO (4764 nm) on the ground. The simplicity, tunability. and power scalability of the OPA make it a strong candidate for general planetary lidar instruments, which will offer important information on the origins of the planet's geology, atmosphere, and potential for biology,

  15. U.S. Coast Guard 1995 oil pollution research grants publications : part 2

    DOT National Transportation Integrated Search

    1997-08-01

    The Oil Pollution Research Grants Program was created by the Oil Pollution Act (OPA) of 1990, P.L. 101-380 (OPA 90), 33 U.S.C. 28761(c)(8) and 2761(c)(9). The OPA established a regional research program and authorized those agencies represented on th...

  16. Evaluation of Neisseria Gonorrhoeae Opacity (Opa) Protein Loops as Targets for Passive Vaccination and Investigation of the Role of Opa Proteins During Infection of a Female Host

    DTIC Science & Technology

    2009-08-24

    Bourne, N., R. B. Pyles, D. I. Bernstein, and L. R. Stanberry. 2002. Modification of primary and recurrent genital herpes in guinea pigs by passive...Barratt, T. E. Hoen, and R. A. Cone. 1994. Passive immunization of the vagina protects mice against vaginal transmission of genital herpes ...and investigations into the role of Opa proteins during infection of the female genital tract. We demonstrated antibodies that target conserved Opa

  17. Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts.

    PubMed

    Sin, Jon; Andres, Allen M; Taylor, David J R; Weston, Thomas; Hiraumi, Yoshimi; Stotland, Aleksandr; Kim, Brandon J; Huang, Chengqun; Doran, Kelly S; Gottlieb, Roberta A

    2016-01-01

    Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Differentiation of primitive myoblasts into mature myotubes requires a metabolic switch to support the increased energetic demand of contractile muscle. Skeletal myoblasts specifically shift from a highly glycolytic state to relying predominantly on oxidative phosphorylation (OXPHOS) upon differentiation. We have found that this phenomenon requires dramatic remodeling of the mitochondrial network involving both mitochondrial clearance and biogenesis. During early myogenic differentiation, autophagy is robustly upregulated and this coincides with DNM1L/DRP1 (dynamin 1-like)-mediated fragmentation and subsequent removal of mitochondria via SQSTM1 (sequestosome 1)-mediated mitophagy. Mitochondria are then repopulated via PPARGC1A/PGC-1α (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha)-mediated biogenesis. Mitochondrial fusion protein OPA1 (optic atrophy 1 [autosomal dominant]) is then briskly upregulated, resulting in the reformation of mitochondrial networks. The final product is a myotube replete with new mitochondria. Respirometry reveals that the constituents of these newly established mitochondrial networks are better primed for OXPHOS and are more tightly coupled than those in myoblasts. Additionally, we have found that suppressing autophagy with various inhibitors during differentiation interferes with myogenic differentiation. Together these data highlight the integral role of autophagy and mitophagy in myogenic differentiation.

  18. Development, evaluation and comparison of two independent sampling and analytical methods for ortho-phthalaldehyde vapors and condensation aerosols in air† ‡

    PubMed Central

    2015-01-01

    Two independent sampling and analytical methods for ortho-phthalaldehyde (OPA) in air have been developed, evaluated and compared (1) a reagent-coated solid sorbent HPLC-UV method and (2) an impinger-fluorescence method. In the first method, air sampling is conducted at 1.0 L min−1 with a sampler containing 350 mg of silica gel coated with 1 mg of acidified 2,4-dinitrophenylhydrazine (DNPH). After sampling, excess DNPH in ethyl acetate is added to the sampler prior to storage for 68 hours. The OPA-DNPH derivative is eluted with 4.0 mL of dimethyl sulfoxide (DMSO) for measurement by HPLC with a UV detector set at 3S5 nm. The estimated detection limit is 0.016 µg per sample or 0.067 µg m−3 (0.012 ppb) for a 240 L air sample. Recoveries of vapor spikes at levels of 1.2 to 6.2 µg were 96 to 101%. Recoveries of spikes as mixtures of vapor and condensation aerosols were 97 to 100%. In the second method, air sampling is conducted at 1.0 L mm−1 with a midget impinger containing 10 mL of DMSO solution containing N-acetyl-l-cysteine and ethylenediamine. The fluorescence reading is taken 80 min after the completion of air sampling. Since the time of taking the fluorescence reading is critical, the reading is taken with a portable fluorometer. The estimated detection limit is 0.024 µg per sample or 0.1 µg m−3 (0.018 ppb) for a 240 L air sample. Recoveries of OPA vapor spikes at levels of 1.4 to 5.0 µg per sample were 97 to 105%. Recoveries of spikes as mixtures of vapors and condensation aerosols were 95 to 99%. The collection efficiency for a mixture of vapor and condensation aerosol was 99.4%. The two methods were compared side-by-side in a generation system constructed for producing controlled atmospheres of OPA vapor in air. Average air concentrations of OPA vapor found by both methods agreed within ±10%. PMID:26346658

  19. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

    PubMed Central

    Baburamani, Ana A.; Hurling, Chloe; Stolp, Helen; Sobotka, Kristina; Gressens, Pierre; Hagberg, Henrik; Thornton, Claire

    2015-01-01

    Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. PMID:26393574

  20. Tier 1 and Tier 3 eAdjudication Business Rule Validation

    DTIC Science & Technology

    2018-04-01

    Approved for Public Distribution Defense Personnel and Security Research Center Office of People Analytics OPA-2018-038 PERSEREC-TR-18-06 April...Northrop Grumman Technology Services Leissa C. Nelson, Ph.D. Susan C. Reed Defense Personnel and Security Research Center Office of People Analytics...Defense Personnel and Security Research Center Office of People Analytics 400 Gigling Road, Seaside, CA 93955 OPA-2018-038 PERSEREC-TR-06 April

  1. Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

    PubMed

    Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

    2017-06-26

    To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

  2. Natural history of JSRV in sheep.

    PubMed

    Sharp, J M; DeMartini, J C

    2003-01-01

    Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour of sheep and, rarely, goats that arises from two types of secretory epithelial cell that retain their luxury function of surfactant synthesis and secretion. It is classified as a low-grade adenocarcinoma and is viewed as a good model for epithelial neoplasia because of its morphological resemblance to the human lung tumour, bronchioloalveolar adenocarcinoma. OPA is present in most of the sheep rearing areas of the globe and, in affected flocks, tumours are present in a high proportion of sheep. OPA is associated with the ovine retrovirus, jaagsiekte sheep retrovirus (JSRV), and is transmissible only with inocula that contain JSRV. All sheep contain JSRV-related endogenous viruses, but JSRV is an exogenous virus that is associated exclusively with OPA. JSRV is detected consistently in the lung fluid, tumour and lymphoid tissues of sheep affected by both natural and experimental OPA or unaffected in-contact flockmates and never in sheep from unaffected flocks with no history of the tumour. JSRV replicates principally in the epithelial tumour cells, but also establishes a disseminated infection of several lymphoid cell types, including peripheral blood leukocytes (PBLs). Longitudinal studies in flocks with endemic OPA have revealed JSRV in PBLs before the onset of clinical OPA and even in the absence of discernible lung tumour. The prevalence of JSRV infection is 40%-80%, although only 30% of sheep appear to develop OPA lesions. A unique feature of OPA is the absence of a specific humoral immune response to JSRV, despite the highly productive infection in the lungs and the disseminated lymphoid infection. This feature is associated with reduced responsiveness to some mitogens, although the phenotypic profile of the peripheral blood remains unaltered. The reduced response is an early and sustained event during infection and may indicate that the failure of infected sheep to produce specific antibodies to JSRV is a direct consequence of infection.

  3. Astigmatism transfer phenomena in the optical parametric amplification process

    NASA Astrophysics Data System (ADS)

    Li, Wenkai; Chen, Yun; Li, Yanyan; Xu, Yi; Guo, Xiaoyang; Lu, Jun; Leng, Yuxin

    2017-01-01

    We numerically and experimentally investigate the astigmatism transfer phenomena in femtosecond optical parametric amplification (OPA). We model the OPA process based on the coupled second-order three-wave nonlinear propagation equations. The numerical and experimental results support that the input pump pulse astigmatism can be transferred into the idler pulse but not the signal pulse, and the idler pulse astigmatism originating from spatial walk-off is less than the idler pulse astigmatism received from the pump. Thus, we can provide a clear understanding of astigmatism transfer mechanisms in the OPA process, and make better use of broadband tunable OPA sources.

  4. Inflammatory effects induced by selected limonene oxidation products: 4-OPA, IPOH, 4-AMCH in human bronchial (16HBE14o-) and alveolar (A549) epithelial cell lines.

    PubMed

    Lipsa, Dorelia; Leva, Paolo; Barrero-Moreno, Josefa; Coelhan, Mehmet

    2016-11-16

    Limonene, a monoterpene abundantly present in most of the consumer products (due to its pleasant citrus smell), easily undergoes ozonolysis leading to several limonene oxidation products (LOPs) such as 4-acetyl-1-methylcyclohexene (4-AMCH), 4-oxopentanal (4-OPA) and 3-isopropenyl-6-oxoheptanal (IPOH). Toxicological studies have indicated that human exposure to limonene and ozone can cause adverse airway effects. However, little attention has been paid to the potential health impact of specific LOPs, in particular of IPOH, 4-OPA and 4-AMCH. This study evaluates the cytotoxic effects of the selected LOPs on human bronchial epithelial (16HBE14o-) and alveolar epithelial (A549) cell lines by generating concentration-response curves using the neutral red uptake assay and analyzing the inflammatory response with a series of cytokines/chemokines. The cellular viability was mostly reduced by 4-OPA [IC 50 =1.6mM (A549) and 1.45mM (16HBE14o-)] when compared to IPOH [IC 50 =3.5mM (A549) and 3.4mM (16HBE14o-)] and 4-AMCH [IC 50 could not be calculated]. As a result from the inflammatory response, IPOH [50μM] induced an increase of both IL-6 and IL-8 secretion in A549 (1.5-fold change) and in 16HBE14o- (2.8- and 7-fold change respectively). 4-OPA [50μM] treatment of A549 increased IL-6 (1.4-times) and IL-8 (1.3-times) levels, while in 16HBE14o- had an opposite effect. A549 treated with 4-AMCH [50μM] elevate both IL-6 and IL-8 levels by 1.2-times, while in 16HBE14o- had an opposite effect. Based on our results, lung cellular injury characterized by inflammatory cytokine release was observed for both cell lines treated with the selected chemicals at concentrations that did not affect their cellular viability. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. Development of High-Fill-Factor Large-Aperture Micromirrors for Agile Optical Phased Arrays

    DTIC Science & Technology

    2010-02-28

    Final Project Report Contract/Grant Title: Development of High-Fill-Factor Large-Aperture Micromirrors for Agile Optical Phased Arrays...factor (HFF) micromirror array (MMA) has been proposed, fabricated and tested. Optical-phased-array (OPA) beam steering based on the HFF MMA has also...electrically tuned to multiple 2. 1. Background High-fill-factor (HFF) micromirror arrays (MMAs) can form optical phased arrays (OPAs) for laser beam

  6. Body mass index: different nutritional status according to WHO, OPAS and Lipschitz classifications in gastrointestinal cancer patients.

    PubMed

    Barao, Katia; Forones, Nora Manoukian

    2012-01-01

    The body mass index (BMI) is the most common marker used on diagnoses of the nutritional status. The great advantage of this index is the easy way to measure, the low cost, the good correlation with the fat mass and the association to morbidity and mortality. To compare the BMI differences according to the WHO, OPAS and Lipschitz classification. A prospective study on 352 patients with esophageal, gastric or colorectal cancer was done. The BMI was calculated and analyzed by the classification of WHO, Lipschitz and OPAS. The mean age was 62.1 ± 12.4 years and 59% of them had more than 59 years. The BMI had not difference between the genders in patients <59 years (P = 0.75), but over 59 years the BMI was higher in women (P<0.01). The percentage of undernourished was 7%, 18% and 21% (P<0.01) by WHO, Lipschitz and OPAS, respectively. The overweight/obesity was also different among the various classifications (P<0.01). Most of the patients with gastrointestinal cancer had more than 65 years. A different cut off must be used for this patients, because undernourished patients may be wrongly considered well nourished.

  7. 2016 Military Investigation and Justice Experience Survey: Overview Report

    DTIC Science & Technology

    2017-05-01

    2016 Military Investigation and Justice Experience Survey (MIJES) Overview Report Additional copies of this report may be obtained from...dtic/order.html Ask for report by DTIC # OPA Report No. 2017-003 March 2017 2016 MILITARY INVESTIGATION AND JUSTICE EXPERIENCE SURVEY (MIJES...Justice Experience Survey (MIJES) 2017 ii | OPA Acknowledgments The Office of People Analytics (OPA) is indebted to numerous people for their

  8. Determination of ammonium ion by fluorometry or spectrophotometry after on-line derivatization with o-phthalaldehyde

    NASA Technical Reports Server (NTRS)

    Goyal, S. S.; Rains, D. W.; Huffaker, R. C.

    1988-01-01

    A fast, sensitive, simple, and highly reproducible method for routine assay of ammonium ion (NH4+) was developed by using HPLC equipment. The method is based on the reaction of NH4+ with o-phthalaldehyde (OPA) in the presence of 2-mercaptoethanol. After an on-line derivatization, the resulting NH4(+)-OPA product was quantified by using fluorometric or spectrophotometric detection. For fluorometric detection, the excitation and emission wavelengths were 410 and 470 nm, respectively. The spectrophotometric detection was made by measuring absorbance at 410 nm. Results on the effects of OPA-reagent composition and pH, reaction temperature, sample matrix, and linearity of the assay are presented. Even though it took about 2 min from the time of sample injection to the appearance of sample peak, sample injections could be overlapped at an interval of about 1 min. Thus, the actual time needed for analysis was about 1 min per assay. The method can be used in a fully automated mode by using an autosampler injector.

  9. Ghost imaging via optical parametric amplification

    NASA Astrophysics Data System (ADS)

    Li, Hong-Guo; Zhang, De-Jian; Xu, De-Qin; Zhao, Qiu-Li; Wang, Sen; Wang, Hai-Bo; Xiong, Jun; Wang, Kaige

    2015-10-01

    We investigate theoretically and experimentally thermal light ghost imaging where the light transmitted through the object as the seed light is amplified by an optical parametric amplifier (OPA). In conventional lens imaging systems with OPA, the spectral bandwidth of OPA dominates the image resolution. Theoretically, we prove that in ghost imaging via optical parametric amplification (GIOPA) the bandwidth of OPA will not affect the image resolution. The experimental results show that for weak seed light the image quality in GIOPA is better than that of conventional ghost imaging. Our work may be valuable in remote sensing with ghost imaging technique, where the light passed through the object is weak after a long-distance propagation.

  10. Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation*

    PubMed Central

    Agarwal, Swati; Yadav, Anuradha; Tiwari, Shashi Kant; Seth, Brashket; Chauhan, Lalit Kumar Singh; Khare, Puneet; Ray, Ratan Singh

    2016-01-01

    The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU- and β-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPA-mediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp-1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus. PMID:27252377

  11. 2017 Workplace and Gender Relations Survey of Reserve Component Members: Overview Report

    DTIC Science & Technology

    2018-04-30

    2017 Workplace and Gender Relations Survey of Reserve Component Members DoD Overview Report Additional copies of this report may be...www.dtic.mil/dtic/order.html Ask for report by DTIC# OPA Report No. 2018-026 April 2018 2017 Workplace and Gender Relations Survey of...OPA) 4800 Mark Center Drive, Suite 06E22, Alexandria, VA 22350-4000 OPA 2017 Workplace and Gender Relations Survey of Reserve Component Members ii

  12. Typing of mutans streptococci by arbitrarily primed polymerase chain reaction.

    PubMed

    Saarela, M; Hannula, J; Mättö, J; Asikainen, S; Alaluusua, S

    1996-01-01

    The discriminative power of the arbitrarily primed polymerase chain reaction (AP-PCR) in differentiating between Streptococcus mutans and Strep. sobrinus species, serotypes and clones was investigated. Mutans streptococcal isolates (12(7)) obtained from 65 individuals (1-10 isolates per individual) were AP-PCR typed separately with two random primers, OPA-05 and OPA-13. Bacterial cell lysates were used as a template in PCR reactions, which made AP-PCR easy and fast to perform. Eighty-one isolates from 19 individuals were also ribotyped to compare the discriminative ability of ribotyping and AP-PCR techniques. AP-PCR performed with the two primers differentiated between Strep. mutans and Strep. sobrinus isolates, but neither primer detected serotype-specific amplification products. OPA-05 distinguished two main AP-PCR patterns among Strep. mutans isolates and one main pattern among Strep. sobrinus isolates, whereas OPA-13 found one main AP-PCR pattern among Strep. mutans isolates and two main patterns among Strep. sobrinus isolates. Ribotyping and AP-PCR revealed 40 and 33 different types among 81 selected isolates, respectively. Both techniques detected intra-individual heterogeneity in 16 out of 19 participants. The results indicate that AP-PCR has good discriminative ability in differentiating between mutans streptococcal clones and that the technique is suitable for epidemiological studies on mutans streptococci.

  13. A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy

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

    Zhang, Juanjuan; Yuan, Yimin; Lin, Bing

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer We report the characterization of a four-generation large Chinese family with ADOA. Black-Right-Pointing-Pointer We find a new heterozygous mutation c.C1198G in OPA1 gene which may be a novel pathogenic mutation in this pedigree. Black-Right-Pointing-Pointer We do not find any mitochondrial DNA mutations associated with optic atrophy. Black-Right-Pointing-Pointer Other factors may also contribute to the phenotypic variability of ADOA in this pedigree. -- Abstract: A large four-generation Chinese family with autosomal dominant optic atrophy (ADOA) was investigated in the present study. Eight of the family members were affected in this pedigree. The affected family members exhibited early-onset and progressivemore » visual impairment, resulting in mild to profound loss of visual acuity. The average age-at-onset was 15.9 years. A new heterozygous mutation c.C1198G was identified by sequence analysis of the 12th exon of the OPA1 gene. This mutation resulted in a proline to alanine substitution at codon 400, which was located in an evolutionarily conserved region. This missense mutation in the GTPase domain was supposed to result in a loss of function for the encoded protein and act through a dominant negative effect. No other mutations associated with optic atrophy were found in our present study. The c.C1198G heterozygous mutation in the OPA1 gene may be a novel key pathogenic mutation in this pedigree with ADOA. Furthermore, additional nuclear modifier genes, environmental factors, and psychological factors may also contribute to the phenotypic variability of ADOA in this pedigree.« less

  14. A large animal model to evaluate the effects of Hsp90 inhibitors for the treatment of lung adenocarcinoma

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

    Varela, Mariana; Golder, Matthew; Archer, Fabienne

    2008-02-05

    Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The JSRV envelope glycoprotein (Env) functions as a dominant oncoprotein in vitro and in vivo. In order to develop the basis for the use of OPA as a lung cancer model, we screened a variety of signal transduction inhibitors for their ability to block transformation by the JSRV Env. Most inhibitors were not effective in blocking JSRV Env-induced transformation. On the contrary, various Hsp90 inhibitors efficiently blocked JSRV transformation. This phenomenon was at least partly due to Akt degradation, which is activatedmore » in JSRV-transformed cells. Hsp90 was found expressed in tumor cells of sheep with naturally occurring OPA. In addition, Hsp90 inhibitors specifically inhibited proliferation of immortalized and moreover primary cells derived from OPA tumors. Thus, OPA could be used as a large animal model for comprehensive studies investigating the effects of Hsp90 inhibitors in lung adenocarcinoma.« less

  15. An evaluation of the effects of eyeball structure on ocular pulse amplitude in healthy subjects.

    PubMed

    Ishii, Kotaro; Mori, Mikiro; Oshika, Tetsuro

    2012-12-01

    To evaluate the effects of eyeball structure on ocular pulse amplitude (OPA) measured using dynamic contour tonometer (DCT). In 86 eyes of 43 healthy subjects, we measured OPA and intraocular pressure (IOP) with DCT (DCT-IOP), IOP with Goldmann applanation tonometry (GAT-IOP), central corneal thickness (CCT), corneal thickness 2 mm (2 mmCT) and 4 mm (4 mmCT) apart from the center, corneal volume within a 3.5-mm radius from the corneal center, corneal curvature, anterior chamber depth, anterior chamber volume, and axial length (AL). OPA had a significant positive correlation with GAT-IOP (Pearson's r = 0.412, p < 0.001), DCT-IOP (r = 0.350, p < 0.001), and 4 mmCT (r = 0.244, p = 0.0231), and had a significant negative correlation with AL (r = -0.268, p = 0.0122). In a multiple linear regression analysis, AL and GAT-IOP were significantly associated with OPA. OPA measured with DCT is significantly influenced by several factors, such as IOP, peripheral corneal thickness (4 mmCT), and AL.

  16. Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program.

    PubMed

    Khacho, Mireille; Clark, Alysen; Svoboda, Devon S; Azzi, Joelle; MacLaurin, Jason G; Meghaizel, Cynthia; Sesaki, Hiromi; Lagace, Diane C; Germain, Marc; Harper, Mary-Ellen; Park, David S; Slack, Ruth S

    2016-08-04

    Regulated mechanisms of stem cell maintenance are key to preventing stem cell depletion and aging. While mitochondrial morphology plays a fundamental role in tissue development and homeostasis, its role in stem cells remains unknown. Here, we uncover that mitochondrial dynamics regulates stem cell identity, self-renewal, and fate decisions by orchestrating a transcriptional program. Manipulation of mitochondrial structure, through OPA1 or MFN1/2 deletion, impaired neural stem cell (NSC) self-renewal, with consequent age-dependent depletion, neurogenesis defects, and cognitive impairments. Gene expression profiling revealed ectopic expression of the Notch self-renewal inhibitor Botch and premature induction of transcription factors that promote differentiation. Changes in mitochondrial dynamics regulate stem cell fate decisions by driving a physiological reactive oxygen species (ROS)-mediated process, which triggers a dual program to suppress self-renewal and promote differentiation via NRF2-mediated retrograde signaling. These findings reveal mitochondrial dynamics as an upstream regulator of essential mechanisms governing stem cell self-renewal and fate decisions through transcriptional programming. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

    PubMed Central

    Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

    2016-01-01

    Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

  18. Addressing the immunopathogenesis of atopic dermatitis: advances in topical and systemic treatment.

    PubMed

    Eichenfield, Lawrence F; Stein Gold, Linda F

    2017-03-01

    Several immunologic mediators-phosphodiesterase (PDE), interleukin (IL), small molecules, and Janus kinase-have been implicated in the pathogenesis of atopic dermatitis, and evidence has shown that blocking these mediators can help modify the disease process. Several new topical medications have been developed that target the enzyme PDE; crisaborole was recently approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis, and phase II studies have been completed on OPA-15406. The phase III clinical trial results of the systemic medication dupilumab, an inhibitor of the IL-4 receptor α subunit (which inhibits both IL-4 and IL-13 signaling), are currently being reviewed by the FDA. ©2017 Frontline Medical Communications.

  19. Dicalcium phosphate (CaHPO4·2H2O) precipitation through ortho- or meta-phosphoric acid-etching: effects on the durability and nanoleakage/ultra-morphology of resin-dentine interfaces.

    PubMed

    Feitosa, Victor Pinheiro; Bazzocchi, Maria Giulia; Putignano, Angelo; Orsini, Giovanna; Luzi, Arlinda Luzi; Sinhoreti, Mário Alexandre Coelho; Watson, Timothy F; Sauro, Salvatore

    2013-11-01

    To compare the effects of two etching procedures using meta-phosphoric (MPA) or ortho-phosphoric acid (OPA) on dentine demineralisation, resin-dentine bonds durability and interface nanoleakage/ultra-morphology. Middle-dentine specimens were etched using 37% OPA (15s) or 40% MPA (60s) and submitted to infrared spectroscopy (FTIR) or ultra-morphology dye-assisted (calcium-staining) confocal microscopy (Ca-CLSM). A three-step etch-and-rinse adhesive was formulated, applied onto dentine and light-cured for 30s before composite build-up. After 24h, the dentine-bonded specimens were cut into 1mm(2) beams; half were immediately submitted to microtensile bond strength (μTBS) and half stored in DW for six months. The μTBS results were analysed with repeated-measures ANOVA and Tukey's test (p<0.05). Further teeth were bonded and prepared for interface nanoleakage/ultra-morphology confocal evaluation. FTIR and Ca-CLSM analyses showed dicalcium phosphate dihydrate (Brushite) precipitation in MPA-etched dentine and on the bottom (front of demineralisation) of the OPA-etched dentine. Statistical analysis showed similar μTBS for both etching procedures after 24h. The μTBS of specimens in OPA-group dropped significantly (p<0.05) after six month; the specimens in the MPA group showed no statistically difference (p>0.05). CLSM depicted no evident sign of nanoleakage within the resin-dentine interface of the MPA-treated specimens, while the specimens in OPA-group presented intense nanoleakage and interface degradation. The use of MPA (60s) as an alternative dentine conditioning agent in etch-and-rinse bonding procedures may be a suitable strategy to create more durable resin-dentine bonds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Determination of (alpha)-dialkylamino acids and their Enantiomers in Geological Samples by High-Performance Liquid Chromatography after Dervatization with a Chiral Adduct of (omicron)-Phthaldialdehyde

    NASA Technical Reports Server (NTRS)

    Zhoa, Meixun; Bada, Jeffrey L.

    1995-01-01

    Derivatization with (omicron)-phthaldialdehyde (OPA) and the chiral thiol N-acetyl-L-cysteine (NAC) is a convenient and sensitive technique for the HPLC detection and resolution of protein amino acid enantiomers. The kinetics of the reaction of OPA-NAC with (alpha)-dialkylamino acids was investigated. The fluorescence yield of (alpha)-dialkylamino acids was only about 10% of that of protein amino acids when the derivatization was carried out at room temperature for 1-2 min, which is the procedure generally used for protein amino acid analyses. The fluorescence yield of (alpha)-dialkylamino acids can be enhanced by up to ten-fold when the derivatization reaction time is increased to 15 min at room temperature. The OPA-NAC technique was optimized for the detection and enantiomeric resolution of a-dialkylamino acids in geological samples which contain a large excess of protein amino acids. The estimated detection limit for a-dialkylamino acids is 1-2 pmol, comparable to that for protein amino acids.

  1. H-NS regulates the Vibrio parahaemolyticus type VI secretion system 1

    PubMed Central

    Salomon, Dor; Klimko, John A.

    2014-01-01

    The marine bacterium Vibrio parahaemolyticus, a major cause of food-borne gastroenteritis, employs a type VI secretion system 1 (T6SS1), a recently discovered protein secretion system, to combat competing bacteria. Environmental signals such as temperature, salinity, cell density and surface sensing, as well as the quorum-sensing master regulator OpaR, were previously reported to regulate T6SS1 activity and expression. In this work, we set out to identify additional transcription regulators that control the tightly regulated T6SS1 activity. To this end, we determined the effect of deletions in several known virulence regulators and in two regulators encoded within the T6SS1 gene cluster on expression and secretion of the core T6SS component Hcp1 and on T6SS1-mediated anti-bacterial activity. We report that VP1391 and VP1407, transcriptional regulators encoded within the T6SS1 gene cluster, are essential for T6SS1 activity. Moreover, we found that H-NS, a bacterial histone-like nucleoid structuring protein, which mediates transcription silencing of horizontally acquired genes, serves as a repressor of T6SS1. We also show that activation of surface sensing and high salt conditions alleviate the H-NS-mediated repression. Our results shed light on the complex network of environmental signals and transcription regulators that govern the tight regulation over T6SS1 activity. PMID:24987102

  2. Ozonolysis at vegetation surfaces. a source of acetone, 4-oxopentanal, 6-methyl-5-hepten-2-one, and geranyl acetone in the troposphere

    NASA Astrophysics Data System (ADS)

    Fruekilde, P.; Hjorth, J.; Jensen, N. R.; Kotzias, D.; Larsen, B.

    The present study gives a possible explanation for the ubiquitous occurrence of 6-methyl-5-hepten-2-one and acetone in ambient air and reports for the first time on a widespread occurrence of geranyl acetone and 4-oxopentanal. We have conducted a series of laboratory experiments in which it is demonstrated that significant amounts of geranyl acetone, 6-methyl-5-hepten-2-one (6-MHO), 4-oxopentanal (4-OPA), and acetone are formed by the reaction of ozone with foliage of common vegetation in the Mediterranean area ( Quercus ilex>Citrus sinensis>Quercus suber>Quercus freinetto>Pinus pinea). In order to rule out biological formation, epicuticular waxes were extracted from the leaves, dispersed on glass wool and allowed to react with a flow of artificial air. Significant amounts of 6-MHO and 4-OPA were formed at ozone concentrations of 50-100 ppbv, but not at zero ozone. A number of terpenoids common in vegetation contain the structural element necessary for ozonolytic formation of 6-MHO. Two sesquiterpenes (nerolidol; farnesol), and a triterpene (squalene) selected as representative test compounds were demonstrated to be strong precursors for acetone, 4-OPA, and 6-MHO. Squalene was also a strong precursor for geranyl acetone. The atmospheric lifetime of geranyl acetone and 6-MHO is less than 1 h under typical conditions. For the present study, we have synthesized 4-OPA and investigated the kinetics of its gas-phase reaction with OH, NO 3, and O 3. A tropospheric lifetime longer than 17 h under typical conditions was calculated from the measured reaction rate constants, which explains the tropospheric occurrence of 4-OPA. It is concluded that future atmospheric chemistry investigations should included geranyl acetone, 6-MHO, and 4-OPA. In a separate experiment it was demonstrated that human skin lipid which contains squalene as a major component is a strong precursor for the four above-mentioned compounds plus nonanal and decanal. The accidental touching of material which later comes into contact with ozone can lead to strong artifact formation of these carbonyl compounds. Previously published results on these compounds must be seen in this new light.

  3. Work–Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress

    PubMed Central

    Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

    2018-01-01

    After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work–family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work–family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work–family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women’s perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work–family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work–family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress. PMID:29719522

  4. Work-Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress.

    PubMed

    Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

    2018-01-01

    After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work-family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work-family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work-family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women's perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work-family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work-family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress.

  5. Target Detection of Quantum Illumination Receiver Based on Photon-subtracted Entanglement State

    NASA Astrophysics Data System (ADS)

    Chi, Jiao; Liu, HongJun; Huang, Nan; Wang, ZhaoLu

    2017-12-01

    We theoretically propose a quantum illumination receiver based on the ideal photon-subtracted two-mode squeezed state (PSTMSS) to efficiently detect the noise-hidden target. This receiver is generated by applying an optical parametric amplifier (OPA) to the cross correlation detection. With analyzing the output performance, it is found that OPA as a preposition technology of the receiver can contribute to the PSTMSS by significantly reducing the error probability than that of the general two-mode squeezed state (TMSS). Comparing with TMSS, the signal-to-noise ratio of quantum illumination based on ideal PSTMSS and OPA is improved more than 4 dB under an optimal gain of OPA. This work may provide a potential improvement in the application of accurate target detection when two kinds of resource have the identical real squeezing parameter.

  6. The usability of the optical parametric amplification of light for high-angular-resolution imaging and fast astrometry

    NASA Astrophysics Data System (ADS)

    Kurek, A. R.; Stachowski, A.; Banaszek, K.; Pollo, A.

    2018-05-01

    High-angular-resolution imaging is crucial for many applications in modern astronomy and astrophysics. The fundamental diffraction limit constrains the resolving power of both ground-based and spaceborne telescopes. The recent idea of a quantum telescope based on the optical parametric amplification (OPA) of light aims to bypass this limit for the imaging of extended sources by an order of magnitude or more. We present an updated scheme of an OPA-based device and a more accurate model of the signal amplification by such a device. The semiclassical model that we present predicts that the noise in such a system will form so-called light speckles as a result of light interference in the optical path. Based on this model, we analysed the efficiency of OPA in increasing the angular resolution of the imaging of extended targets and the precise localization of a distant point source. According to our new model, OPA offers a gain in resolved imaging in comparison to classical optics. For a given time-span, we found that OPA can be more efficient in localizing a single distant point source than classical telescopes.

  7. Fine mapping of the rice Bph1 gene, which confers resistance to the brown planthopper (Nilaparvata lugens stal), and development of STS markers for marker-assisted selection.

    PubMed

    Cha, Young-Soon; Ji, Hyeonso; Yun, Doh-Won; Ahn, Byoung-Ohg; Lee, Myung Chul; Suh, Seok-Cheol; Lee, Chun Seok; Ahn, Eok Keun; Jeon, Yong-Hee; Jin, Il-Doo; Sohn, Jae-Keun; Koh, Hee-Jong; Eun, Moo-Young

    2008-08-31

    The brown planthopper (BPH) is a major insect pest in rice, and damages these plants by sucking phloem-sap and transmitting viral diseases. Many BPH resistance genes have been identified in indica varieties and wild rice accessions, but none has yet been cloned. In the present study we report fine mapping of the region containing the Bph1 locus, which enabled us to perform marker-aided selection (MAS). We used 273 F8 recombinant inbred lines (RILs) derived from a cross between Cheongcheongbyeo, an indica type variety harboring Bph1 from Mudgo, and Hwayeongbyeo, a BPH susceptible japonica variety. By random amplification of polymorphic DNA (RAPD) analysis using 656 random 10-mer primers, three RAPD markers (OPH09, OPA10 and OPA15) linked to Bph1 were identified and converted to SCAR (sequence characterized amplified region) markers. These markers were found to be contained in two BAC clones derived from chromosome 12: OPH09 on OSJNBa0011B18, and both OPA10 and OPA15 on OSJNBa0040E10. By sequence analysis of ten additional BAC clones evenly distributed between OSJNBa0011B18 and OSJNBa0040E10, we developed 15 STS markers. Of these, pBPH4 and pBPH14 flanked Bph1 at distances of 0.2 cM and 0.8 cM, respectively. The STS markers pBPH9, pBPH19, pBPH20, and pBPH21 co-segregated with Bph1. These markers were shown to be very useful for marker-assisted selection (MAS) in breeding populations of 32 F6 RILs from a cross between Andabyeo and IR71190, and 32 F5 RILs from a cross between Andabyeo and Suwon452.

  8. Natural Resource Damages: Trustees

    EPA Pesticide Factsheets

    CERCLA and OPA authorize the United States, States, and Indian Tribes to act on behalf of the public as Natural Resource Trustees for natural resources under their respective trusteeship. OPA also authorizes foreign governments to act as Trustees.

  9. OEI and OPA Issue a Joint Memorandum of Understanding (2002 Memo)

    EPA Pesticide Factsheets

    This MOU delineates certain interdependent functions, oversight responsibilities, and joint initiatives of the Office of Public Affairs (OPA) and the Office of Environmental Information (OEI) for the Agency's public Web site.

  10. Association of occupational activity with joint space narrowing and osteophytosis in the medial compartment of the knee: the ROAD study (OAC5914R2).

    PubMed

    Muraki, S; Oka, H; Akune, T; En-yo, Y; Yoshida, M; Nakamura, K; Kawaguchi, H; Yoshimura, N

    2011-07-01

    We investigated the association of occupational activity with joint space narrowing and osteophytosis at the knee separately in Japanese subjects using a large-scale population-based cohort of the Research on Osteoarthritis Against Disability (ROAD). From the baseline survey of the ROAD study, 1,402 participants (512 men and 890 women) living in mountainous and seacoast communities were analyzed. Information collected included a lifetime occupational history and details of specific workplace physical activities. To estimate the severity of joint space narrowing and osteophytosis at the knee, minimum joint space width (mJSW) and osteophyte area (OPA) in the medial compartment of the knee were measured using a knee osteoarthritis (OA) computer-aided diagnosis system. For women, agricultural, forestry, and fishery workers had significantly lower mJSW values compared with clerical workers or technical experts, whereas OPA did not differ significantly among job titles in men or women. For occupational activities, kneeling and squatting were associated with lower mJSW as well as higher OPA. Walking and heavy lifting were associated with lower mJSW, but not with OPA. This cross-sectional study using a population-based cohort suggests that an occupational activity that includes kneeling and squatting appears to have a greater effect on knee OA. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. Evaluation of genetic variability in micropropagated propagules of ornamental pineapple [Ananas comosus var. bracteatus (Lindley) Coppens and Leal] using RAPD markers.

    PubMed

    Santos, M D M; Buso, G C S; Torres, A C

    2008-10-21

    The objective of the present study was to evaluate the genetic variability in micropropagated plantlets of ornamental pineapple, after the fourth period of subculture. The basal culture medium consisted of MS salts, vitamins, 3% sucrose, liquid formulation, supplemented with 6-benzylaminopurine (BAP) at concentrations of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L. The addition of BAP influenced the occurrence of genetic variation revealed using random amplified polymorphic DNA (RAPD) markers. Of a total of 520 primers tested, 44 were selected and amplified; 402 monomorphic bands (97.2%) and 18 polymorphic bands (2.8%) resulted among regenerated plantlets. The polymorphic fragments were produced by 12 primers (OPA-01, OPA-20, OPB-01, OPB-19, OPC-19, OPF-13, OPL-17, OPM-13, OPP-16, OPT-07, OPV-19, and OPX-03). Among the primers that identified polymorphism, OPA-01, OPA-20, OPB-19, OPC-19, OPL-17, OPP-16, and OPX-3 each showed, one polymorphic band and OPF-13 amplified a maximum of three bands. In this study, the RAPD technique was effective in showing the occurrence of somaclonal variations that occur during the micropropagation process of ornamental pineapple cultivation in BAP-supplemented medium, and it is possible to detect the presence of genetic variation in early stages of plant development.

  12. A misleading false-negative result using Neisseria gonorrhoeae opa MGB multiplex PCR assay in patient's rectal sample due to partial mutations of the opa gene.

    PubMed

    Vahidnia, Ali; van Empel, Pieter Jan; Costa, Sandra; Oud, Rob T N; van der Straaten, Tahar; Bliekendaal, Harry; Spaargaren, Joke

    2015-07-01

    A 53-year-old homosexual man presented at his general practitioner (GP) practice with a suspicion of sexually transmitted infection. Initial NAAT screening was performed for Chlamydia trachomatis and Neisseria gonorrhoeae. The patient was positive for Neisseria gonorrhoeae both for his urine and rectal sample. The subsequent confirmation test for Neisseria gonorrhoeae by a second laboratory was only confirmed for the urine sample and the rectal sample was negative. We report a case of a potential false-negative diagnosis of Neisseria gonorrhoeae due to mutations of DNA sequence in the probe region of opa-MGB assay of the rectal sample. The patient did not suffer any discomfort as diagnosis of Neisseria gonorrhoeae in his urine sample had already led to treatment by prescribing the patient with Ceftriaxone 500 mg IV dissolved in 1 ml lidocaine 2% and 4 mL saline. The patient also received a prescription for Azithromycin (2x500 mg).

  13. Recurrence of Lower Urinary Tract Symptoms Following Prostate Artery Embolization for Benign Hyperplasia: Single Center Experience Comparing Two Techniques

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

    Carnevale, Francisco Cesar, E-mail: francisco.carnevale@criep.com.br; Moreira, Airton Mota; Harward, Sardis Honoria

    PurposeTo compare recurrence of lower urinary tract symptoms (LUTS) recurrence at 12 months following original prostate artery embolization (oPAE) or “proximal embolization first, then embolize distal” (PErFecTED) PAE for benign prostatic hyperplasia (BPH).Materials and Methods105 consecutive patients older than 45 years, with prostate size greater than 30 cm{sup 3}, International Prostate Symptom Score (IPSS) ≥ 8, quality of life (QoL) index ≥ 3, and refractory status or intolerance of medical management were prospectively enrolled between June 2008 and August 2013. The study was IRB-approved, and all patients provided informed consent. Patients underwent oPAE or PErFecTED PAE and were followed for at least 12 months. Technical success was definedmore » as bilateral embolization and clinical success (non-recurrence) was defined as removal of the Foley catheter in patients with urinary retention, IPSS < 8 and QoL index < 3 at 12 months of follow-up. Nonparametric statistics were used to compare the study groups due to the size of the study population and distributions of clinical data.Results97 patients had 12-month data and were categorized as oPAE without recurrence (n = 46), oPAE with recurrence (n  = 13), PErFecTED without recurrence (n  = 36), or PErFecTED with recurrence (n  = 2). Recurrence was significantly more common in oPAE patients (χ{sup 2}, p = 0.026). Unilateral embolization was significantly associated with recurrence among patients who underwent oPAE (χ{sup 2}, p = 0.032).ConclusionsBoth oPAE and PErFecTED PAE are safe and effective methods for treatment of LUTS, but PErFecTED PAE is associated with a significantly lower rate of symptom recurrence.« less

  14. The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine.

    PubMed

    Chidley, Christopher; Trauger, Sunia A; Birsoy, Kıvanç; O'Shea, Erin K

    2016-07-12

    Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a loss-of-function genetic screen in human haploid KBM7 cells to discover the mechanism of action of the anticancer natural product ophiobolin A (OPA). We found that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization. Our characterization of this unusual cytotoxicity mechanism, made possible by unbiased genetic screening in human cells, suggests that the selective antitumor activity displayed by OPA may be due to altered membrane PE levels in cancer cells.

  15. International Space Station (ISS) Internal Active Thermal Control System (IATCS) New Biocide Selection, Qualification and Implementation

    NASA Technical Reports Server (NTRS)

    Wilson, Mark E.; Cole, Harold E.; Rector, Tony; Steele, John; Varsik, Jerry

    2011-01-01

    The Internal Active Thermal Control System (IATCS) aboard the International Space Station (ISS) is primarily responsible for the removal of heat loads from payload and system racks. The IATCS is a water based system which works in conjunction with the EATCS (External ATCS), an ammonia based system, which are interfaced through a heat exchanger to facilitate heat transfer. On-orbit issues associated with the aqueous coolant chemistry began to occur with unexpected increases in CO2 levels in the cabin. This caused an increase in total inorganic carbon (TIC), a reduction in coolant pH, increased corrosion, and precipitation of nickel phosphate. These chemical changes were also accompanied by the growth of heterotrophic bacteria that increased risk to the system and could potentially impact crew health and safety. Studies were conducted to select a biocide to control microbial growth in the system based on requirements for disinfection at low chemical concentration (effectiveness), solubility and stability, material compatibility, low toxicity to humans, compatibility with vehicle environmental control and life support systems (ECLSS), ease of application, rapid on-orbit measurement, and removal capability. Based on these requirements, ortho-phthalaldehyde (OPA), an aromatic dialdehyde compound, was selected for qualification testing. This paper presents the OPA qualification test results, development of hardware and methodology to safely apply OPA to the system, development of a means to remove OPA, development of a rapid colorimetric test for measurement of OPA, and the OPA on-orbit performance for controlling the growth of microorganisms in the ISS IATCS since November 3, 2007.

  16. International Space Station (ISS) Internal Active Thermal Control System (IATCS) New Biocide Selection, Qualification and Implementation

    NASA Technical Reports Server (NTRS)

    Wilson, Mark E.; Cole, Harold; Rector, Tony; Steele, John; Varsik, Jerry

    2010-01-01

    The Internal Active Thermal Control System (IATCS) aboard the International Space Station (ISS) is primarily responsible for the removal of heat loads from payload and system racks. The IATCS is a water based system which works in conjunction with the EATCS (External ATCS), an ammonia based system, which are interfaced through a heat exchanger to facilitate heat transfer. On-orbit issues associated with the aqueous coolant chemistry began to occur with unexpected increases in CO2 levels in the cabin. This caused an increase in total inorganic carbon (TIC), a reduction in coolant pH, increased corrosion, and precipitation of nickel phosphate. These chemical changes were also accompanied by the growth of heterotrophic bacteria that increased risk to the system and could potentially impact crew health and safety. Studies were conducted to select a biocide to control microbial growth in the system based on requirements for disinfection at low chemical concentration (effectiveness), solubility and stability, material compatibility, low toxicity to humans, compatibility with vehicle environmental control and life support systems (ECLSS), ease of application, rapid on-orbit measurement, and removal capability. Based on these requirements, ortho-phthalaldehyde (OPA), an aromatic dialdehyde compound, was selected for qualification testing. This paper presents the OPA qualification test results, development of hardware and methodology to safely apply OPA to the system, development of a means to remove OPA, development of a rapid colorimetric test for measurement of OPA, and the OPA on-orbit performance for controlling the growth of microorganisms in the ISS IATCS since November 3, 2007.

  17. Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1

    PubMed Central

    Chang, Chuang-Rung; Blackstone, Craig

    2017-01-01

    Mitochondria in cells comprise a tubulovesicular network shaped continuously by complementary fission and fusion events. The mammalian Drp1 protein plays a key role in fission, while Mfn1, Mfn2, and OPA1 are required for fusion. Shifts in the balance between these opposing processes can occur rapidly, indicating that modifications to these proteins may regulate mitochondrial membrane dynamics. We highlight posttranslational modifications of the mitochondrial fission protein Drp1, for which these regulatory mechanisms are best characterized. This dynamin-related GTPase undergoes a number of steps to mediate mitochondrial fission, including translocation from cytoplasm to the mitochondrial outer membrane, higher-order assembly into spirals, GTP hydrolysis associated with a conformational change and membrane deformation, and ultimately disassembly. Many of these steps may be influenced by covalent modification of Drp1. We discuss the dynamic nature of Drp1 modifications and how they contribute not only to the normal regulation of mitochondrial division, but also to neuropathologic processes. PMID:20649536

  18. Cultivating secondary traumatic growth among healthcare workers: the role of social support and self-efficacy.

    PubMed

    Shoji, Kotaro; Bock, Judith; Cieslak, Roman; Zukowska, Katarzyna; Luszczynska, Aleksandra; Benight, Charles C

    2014-09-01

    This 2-study longitudinal investigation examined the indirect effects of secondary traumatic stress (STS) on secondary traumatic growth via two mediators: perceived social support and secondary trauma self-efficacy. In particular, we tested if the 2 hypothetical mediators operate sequentially, that is, with secondary trauma self-efficacy facilitating social support (i.e., cultivation hypothesis) and/or social support enhancing self-efficacy (i.e., enabling hypothesis). Participants in Study 1 (N = 293 at Time 1, N = 115 at Time 2) were behavioral healthcare providers working with U.S. military personnel suffering from trauma. Study 2 was conducted among Polish healthcare workers (N = 298 at Time 1, N = 189 at Time 2) providing services for civilian survivors of traumatic events. In both studies, multiple mediational analyses showed evidence for the cultivation hypothesis. The relationship between STS at Time 1 and secondary traumatic growth at Time 2 was mediated sequentially by secondary trauma self-efficacy at Time 1 and social support at Time 2. The enabling hypothesis was not supported. Education and development programs for healthcare workers may benefit from boosting self-efficacy with the intent to facilitate perceived social support. © 2014 Wiley Periodicals, Inc.

  19. Childhood Maltreatment and PTSD: Spiritual Well-Being and Intimate Partner Violence as Mediators

    PubMed Central

    Zhang, Huaiyu; Pittman, Delishia M.; Lamis, Dorian A.; Fischer, Nicole L.; Schwenke, Tomina J.; Carr, Erika R.; Shah, Sanjay; Kaslow, Nadine J.

    2016-01-01

    Childhood maltreatment places individuals, including African American women who are undereducated and economically disadvantaged, at risk for developing posttraumatic stress disorder (PTSD) symptoms. Participants were 192 African American women with a history in the prior year of both a suicide attempt and intimate partner violence (IPV) exposure. They were recruited from a public hospital that provides medical and mental health treatment to mostly low-income patients. A simple mediator model was used to examine if (1) existential well-being (sense of purpose) and/or religious well-being (relationship with God) mediated the link between childhood maltreatment and adult PTSD symptoms. Sequential multiple mediator models determined if physical and nonphysical IPV enhanced our understanding of the mediational association among the aforementioned variables. Findings suggest that existential well-being mediated the association between childhood maltreatment and adult PTSD symptoms in a simple mediator model, and existential well-being and recent nonphysical IPV served as sequential multiple mediators of this link. However, religious well-being and physical IPV were not significant mediators. Findings underscore the importance of enhancing existential well-being in the treatment of suicidal African American women with a history of childhood maltreatment and IPV. PMID:26989343

  20. Destruction of OPA from munitions demilitarization in supercritical water oxidation: kinetics of total organic carbon disappearance.

    PubMed

    Veriansyah, Bambang; Kim, Jae-Duck; Lee, Jong-Chol; Hong, Deasik

    2006-01-01

    The destruction of OPA from munitions demilitarization has been accomplished in supercritical water oxidation (SCWO) with oxygen as oxidant in an isothermal continuous-flow reactor. The experiments were conducted at a temperature of 689-887 K and a fixed pressure of 25 MPa, with a residence time that ranged from 7 s to 14 s. The destruction efficiency was measured by total organic carbon (TOC) conversion. At the reaction condition, the initial TOC concentrations of OPA were varied from 1.41 mmol/L to 19.57 mmol/L and the oxygen concentrations were varied from 15.03 mmol/L to 81.85 mmol/L. Experimental data showed that all the TOC conversions were >80% under the above experimental conditions. The kinetics of TOC disappearance, which is essential for the design, optimization, and control of reliable commercial SCWO reactor was developed by taking into account the dependence of the oxidant and TOC concentration on the reaction rate. A global TOC disappearance rates expression was regressed from the data of 38 experiments, to a 95% confidence level. The resulting activation energy was determined to be 44.01 +/- 1.52 kJ/mol, and the pre-exponential factor was (1.67 +/- 0.45) x 10(2) L(1.14) mmol(-0.14) s(-1). The reaction orders for the TOC and the oxidant were 0.98 +/- 0.01 and 0.16 +/- 0.02, respectively.

  1. Physiotherapist agreement when visually rating movement quality during lower extremity functional screening tests.

    PubMed

    Whatman, Chris; Hing, Wayne; Hume, Patria

    2012-05-01

    To investigate physiotherapist agreement in rating movement quality during lower extremity functional tests using two visual rating methods and physiotherapists with differing clinical experience. Clinical measurement. Six healthy individuals were rated by 44 physiotherapists. These raters were in three groups (inexperienced, novice, experienced). Video recordings of all six individuals performing four lower extremity functional tests were visually rated (dichotomous or ordinal scale) using two rating methods (overall or segment) on two occasions separated by 3-4 weeks. Intra and inter-rater agreement for physiotherapists was determined using overall percentage agreement (OPA) and the first order agreement coefficient (AC1). Intra-rater agreement for overall and segment methods ranged from slight to almost perfect (OPA: 29-96%, AC1: 0.01 to 0.96). AC1 agreement was better in the experienced group (84-99% likelihood) and for dichotomous rating (97-100% likelihood). Inter-rater agreement ranged from fair to good (OPA: 45-79%; AC1: 0.22-0.71). AC1 agreement was not influenced by clinical experience but was again better using dichotomous rating. Physiotherapists' visual rating of movement quality during lower extremity functional tests resulted in slight to almost perfect intra-rater agreement and fair to good inter-rater agreement. Agreement improved with increased level of clinical experience and use of dichotomous rating. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities.

    PubMed

    Di Pietro, Valentina; Lazzarino, Giacomo; Amorini, Angela Maria; Signoretti, Stefano; Hill, Lisa J; Porto, Edoardo; Tavazzi, Barbara; Lazzarino, Giuseppe; Belli, Antonio

    2017-08-23

    Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.

  3. Target-based coherent beam combining of an optical phased array fed by a broadband laser source

    NASA Astrophysics Data System (ADS)

    Hyde, Milo W., IV; McCrae, Jack E.; Tyler, Glenn A.

    2017-11-01

    The target-based phasing of an optical phased array (OPA) fed by a broadband master oscillator laser source is investigated. The specific scenario examined here considers an OPA phasing through atmospheric turbulence on a rough curved object. An analytical expression for the detected or received intensity is derived. Gleaned from this expression are the conditions under which target-based phasing is possible. A detailed OPA wave optics simulation is performed to validate the theoretical findings. Key aspects of the simulation set-up as well as the results are thoroughly discussed.

  4. Spatial resolution limitation of liquid crystal spatial light modulator

    NASA Astrophysics Data System (ADS)

    Wang, Xinghua; Wang, Bin; McManamon, Paul F., III; Pouch, John J.; Miranda, Felix A.; Anderson, James E.; Bos, Philip J.

    2004-10-01

    The effect of fringing electric fields in a liquid crystal (LC) Optical Phased Array (OPA), also referred to as a spatial light modulator (SLM), is a governing factor that determines the diffraction efficiency (DE) of the LC OPA for high resolution spatial phase modulation. In this article, the fringing field effect in a high resolution LC OPA is studied by accurate modeling the DE of the LC blazed gratings by LC director simulation and Finite Difference Time Domain (FDTD) simulation. Influence factors that contribute significantly to the DE are discussed. Such results provide fundamental understanding for high resolution LC devices.

  5. Effects of Organized Physical Activity on Selected Health Indices among Women Older than 55 Years.

    PubMed

    Zmijewski, Piotr; Mazurek, Krzysztof; Kozdron, Ewa; Szczypiorski, Piotr; Frysztak, Agata

    2015-01-01

    The main aim of this study was to determine health benefits among women older than 55 years who participated in organized, group-based physical activity (OPA). Thirty-five women aged 65.0 ± 7.3 years volunteered for this study. The classical and nonclassical cardiovascular (CVD) risk factors were measured before and after a 2-week OPA camp in a remote location and 3 months of OPA. Self-guided physical activity was analyzed 18 months after OPA. Two-week effects included significant decreases in body mass index, waist and hip circumferences, resting systolic and diastolic blood pressure (BP) and resting heart rate, improved exercise capacity (EC), improved low-density lipoprotein and high-density lipoprotein (HDL-C), cholesterol, and other atherogenic lipid indices (ALI), and a reduction in 10-year estimated risk of death from CVD. Three-month effects included a further decrease in systolic BP, improvements in EC and HDL-C, and maintenance of lower levels of ALI, as well as lower CVD risk. The implementation of the OPA programme had a positive impact on somatic features, exercise capacity, biochemical indices, and risk for death from CVD. The presented programme can be regarded as an effective element of primary prevention of cardiovascular diseases among women older than 55 years.

  6. Orthogonal projection approach and continuous wavelet transform-feed forward neural networks for simultaneous spectrophotometric determination of some heavy metals in diet samples.

    PubMed

    Abbasi Tarighat, Maryam

    2016-02-01

    Simultaneous spectrophotometric determination of a mixture of overlapped complexes of Fe(3+), Mn(2+), Cu(2+), and Zn(2+) ions with 2-(3-hydroxy-1-phenyl-but-2-enylideneamino) pyridine-3-ol(HPEP) by orthogonal projection approach-feed forward neural network (OPA-FFNN) and continuous wavelet transform-feed forward neural network (CWT-FFNN) is discussed. Ionic complexes HPEP were formulated with varying reagent concentration, pH and time of color formation for completion of complexation reactions. It was found that, at 5.0 × 10(-4) mol L(-1) of HPEP, pH 9.5 and 10 min after mixing the complexation reactions were completed. The spectral data were analyzed using partial response plots, and identified non-linearity modeled using FFNN. Reducing the number of OPA-FFNN and CWT-FFNN inputs were simplified using dissimilarity pure spectra of OPA and selected wavelet coefficients. Once the pure dissimilarity plots ad optimal wavelet coefficients are selected, different ANN models were employed for the calculation of the final calibration models. The performance of these two approaches were tested with regard to root mean square errors of prediction (RMSE %) values, using synthetic solutions. Under the working conditions, the proposed methods were successfully applied to the simultaneous determination of metal ions in different vegetable and foodstuff samples. The results show that, OPA-FFNN and CWT-FFNN were effective in simultaneously determining Fe(3+), Mn(2+), Cu(2+), and Zn(2+) concentration. Also, concentrations of metal ions in the samples were determined by flame atomic absorption spectrometry (FAAS). The amounts of metal ions obtained by the proposed methods were in good agreement with those obtained by FAAS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Impact of pH and application time of meta-phosphoric acid on resin-enamel and resin-dentin bonding.

    PubMed

    Cardenas, A F M; Siqueira, F S F; Bandeca, M C; Costa, S O; Lemos, M V S; Feitora, V P; Reis, A; Loguercio, A D; Gomes, J C

    2018-02-01

    To evaluate the immediate microshear resin-enamel bond strength (μSBS) and the immediate and 6-month microtensile bond strength (μTBS) and nanoleakage (NL) of the adhesive interface performed by different pHs of 40% meta-phosphoric acid (MPA) were compared with conventional 37% ortho-phosphoric acid (OPA) under different application times. Additionally, the enamel etching patterns were evaluated and the chemical/morphological changes induced by these differents groups were evaluated. One hundred and ninety-eight extracted human molars were randomly assigned into experimental groups according to the combination of independent variables: Acid [37% ortho-phosphoric acid (OPA), 40% meta-phosphoric acid (MPA) at pHs of: 0.5, 1 and 2] and Application Time [7, 15 and 30s]. Enamel-bond specimens were prepared and tested under μSBS. Resin-dentin beams were tested under μTBS tested immediately or after 6-months of water storage. Nanoleakage was evaluated using bonded-beams of each tooth/time-period. Enamel etching pattern and chemical and ultra-morphology analyses were also performed. The μSBS (MPa) data were subjected to a two-way repeated measures ANOVA (Acid vs. Application time). For μTBS, Acid vs application time vs storage time data were subjected to three-way ANOVA and Tukey's test (α = 0.05). MPA pH 0.5 showed μTBS similar to OPA, independently of the application time on enamel (p>0.05) or dentin (p>0.05). OPA provided higher nanoleakage values than MPA (p = 0.003). Significant decreases in TBS and increases in NL were only observed for OPA after 6 months (p = 0.001). An increase in the application time resulted in a more pronounced etching pattern for MPA. Chemical analysis showed that dentin demineralized by MPA depicted peaks of brushite and octacalcium phosphate. MPA exposed less collagen than OPA. However, optimal results for MPA were dependent on pH/application time. The use of 40% meta-phosphoric acid with a pH of 0.5 is an alternative acid-etching agent for dentin and enamel bonding. Furthermore, the use of MPA preserves the resin-dentin interface over a 6-months period, due to presence of brushite and octacalcium phosphate and a reduced demineralization pattern. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Comparison of Total Dose Effects on Micropower Op-Amps: Bipolar and CMOS

    NASA Technical Reports Server (NTRS)

    Lee, C.; Johnston, A.

    1998-01-01

    This paper compares low-paper op-amps, OPA241 (bipolar) and OPA336 (CMOS), from Burr-Brown, MAX473 (bipolar) and MAX409 (CMOS), characterizing their total dose response with a single 2.7V power supply voltage.

  9. Inactivation of surrogate coronaviruses on hard surfaces by health care germicides.

    PubMed

    Hulkower, Rachel L; Casanova, Lisa M; Rutala, William A; Weber, David J; Sobsey, Mark D

    2011-06-01

    In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  10. Enhancing fatty acid utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing optic atrophy 1 processing in the failing heart.

    PubMed

    Guo, Yongzheng; Wang, Zhen; Qin, Xinghua; Xu, Jie; Hou, Zuoxu; Yang, Hongyan; Mao, Xuechao; Xing, Wenjuan; Li, Xiaoliang; Zhang, Xing; Gao, Feng

    2018-06-01

    Heart failure (HF) is characterized by reduced fatty acid (FA) utilization associated with mitochondrial dysfunction. Recent evidence has shown that enhancing FA utilization may provide cardioprotection against HF. Our aim was to investigate the effects and the underlying mechanisms of cardiac FA utilization on cardiac function in response to pressure overload. Transverse aortic constriction (TAC) was used in C57 mice to establish pressure overload-induced HF. TAC mice fed on a high fat diet (HFD) exhibited increased cardiac FA utilization and improved cardiac function and survival compared with those on control diet. Such cardioprotection could also be provided by cardiac-specific overexpression of CD36. Notably, both HFD and CD36 overexpression attenuated mitochondrial fragmentation and improved mitochondrial function in the failing heart. Pressure overload decreased ATP-dependent metalloprotease (YME1L) expression and induced the proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 as a result of suppressed FA utilization. Enhancing FA utilization upregulated YME1L expression and subsequently rebalanced OPA1 processing, resulting in restoration of mitochondrial morphology in the failing heart. In addition, cardiac-specific overexpression of YME1L exerted similar cardioprotective effects against HF to those provided by HFD or CD36 overexpression. These findings demonstrate that enhancing FA utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing OPA1 processing in pressure overload-induced HF, suggesting a unique metabolic intervention approach to improving cardiac functions in HF.

  11. Towards a petawatt-class few-cycle infrared laser system via dual-chirped optical parametric amplification.

    PubMed

    Fu, Yuxi; Midorikawa, Katsumi; Takahashi, Eiji J

    2018-05-16

    Expansion of the wavelength range for an ultrafast laser is an important ingredient for extending its range of applications. Conventionally, optical parametric amplification (OPA) has been employed to expand the laser wavelength to the infrared (IR) region. However, the achievable pulse energy and peak power have been limited to the mJ and the GW level, respectively. A major difficulty in the further energy scaling of OPA results from a lack of suitable large nonlinear crystals. Here, we circumvent this difficulty by employing a dual-chirped optical parametric amplification (DC-OPA) scheme. We successfully generate a multi-TW IR femtosecond laser pulse with an energy of 100 mJ order, which is higher than that reported in previous works. We also obtain excellent energy scaling ability, ultrashort pulses, flexiable wavelength tunability, and high-energy stability, which prove that DC-OPA is a superior method for the energy scaling of IR pulses to the 10 J/PW level.

  12. A-DROP: A predictive model for the formation of oil particle aggregates (OPAs)

    USGS Publications Warehouse

    Zhao, Lin; Boufadel, Michel C.; Geng, Xiaolong; Lee, Kenneth; King, Thomas; Robinson, Brian; Fitzpatrick, Faith A.

    2016-01-01

    Oil–particle interactions play a major role in removal of free oil from the water column. We present a new conceptual–numerical model, A-DROP, to predict oil amount trapped in oil–particle aggregates. A new conceptual formulation of oil–particle coagulation efficiency is introduced to account for the effects of oil stabilization by particles, particle hydrophobicity, and oil–particle size ratio on OPA formation. A-DROP was able to closely reproduce the oil trapping efficiency reported in experimental studies. The model was then used to simulate the OPA formation in a typical nearshore environment. Modeling results indicate that the increase of particle concentration in the swash zone would speed up the oil–particle interaction process; but the oil amount trapped in OPAs did not correspond to the increase of particle concentration. The developed A-DROP model could become an important tool in understanding the natural removal of oil and developing oil spill countermeasures by means of oil–particle aggregation.

  13. A-DROP: A predictive model for the formation of oil particle aggregates (OPAs).

    PubMed

    Zhao, Lin; Boufadel, Michel C; Geng, Xiaolong; Lee, Kenneth; King, Thomas; Robinson, Brian; Fitzpatrick, Faith

    2016-05-15

    Oil-particle interactions play a major role in removal of free oil from the water column. We present a new conceptual-numerical model, A-DROP, to predict oil amount trapped in oil-particle aggregates. A new conceptual formulation of oil-particle coagulation efficiency is introduced to account for the effects of oil stabilization by particles, particle hydrophobicity, and oil-particle size ratio on OPA formation. A-DROP was able to closely reproduce the oil trapping efficiency reported in experimental studies. The model was then used to simulate the OPA formation in a typical nearshore environment. Modeling results indicate that the increase of particle concentration in the swash zone would speed up the oil-particle interaction process; but the oil amount trapped in OPAs did not correspond to the increase of particle concentration. The developed A-DROP model could become an important tool in understanding the natural removal of oil and developing oil spill countermeasures by means of oil-particle aggregation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Mitochondrial fission contributes to heat-induced oxidative stress in skeletal muscle but not hyperthermia in mice.

    PubMed

    Yu, Tianzheng; Ferdjallah, Iman; Elenberg, Falicia; Chen, Star K; Deuster, Patricia; Chen, Yifan

    2018-05-01

    We have previously demonstrated in vitro that heat-induced skeletal muscle damage is associated with an increase in dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and no change in mitochondrial fusion. In this study, we investigated the in vivo effects of mitochondrial fission inhibition on heat-induced oxidative skeletal muscle injury and hyperthermic response in mice. Core body temperatures of mice pre-treated with vehicle or Mdivi-1 were recorded by radio telemetry during heat exposure. Tissue samples were obtained immediately following heat exposure. We found that heat exposure caused increased mitochondrial fragmentation and mitochondrial fission protein Drp1 expression, whereas had no effect on the mitochondrial fusion-related proteins mitofusin 1, mitofusin 2 and OPA1 in mouse gastrocnemius muscles. Two groups of mice with a similar high level of heat-induced hyperthermia were allowed to recover for at least one week and subsequently treated with Mdivi-1 and vehicle, respectively. Neither Mdivi-1 nor vehicle altered the hyperthermic responses of mice during heat exposure. However, Mdivi-1 significantly reduced mitochondrial fragmentation and Drp1, reactive oxygen species levels and apoptotic responses in mouse gastrocnemius muscles following heat exposure compared with vehicle. These results suggest that Drp1-mediated mitochondrial fission plays a role in heat-induced oxidative stress in skeletal muscle, but not in hyperthermic response in mice. Published by Elsevier Inc.

  15. Simulation of a current source with a Cole-Cole load for multi-frequency electrical impedance tomography.

    PubMed

    Aguiar Santos, Susana; Schlebusch, Thomas; Leonhardt, Steffen

    2013-01-01

    An accurate current source is one of the keys in the hardware of Electrical impedance Tomography systems. Limitations appear mainly at higher frequencies and for non-simple resistive loads. In this paper, we simulate an improved Howland current source with a Cole-Cole load. Simulations comparing two different op-amps (THS4021 and OPA843) were performed at 1 kHz to 1 MHz. Results show that the THS4021 performed better than the OPA843. The current source with THS4021 reaches an output impedance of 20 MΩ at 1 kHz and above 320 kΩ at 1 MHz, it provides a constant and stable output current up to 4 mA, in the complete range of frequencies, and for Cole-Cole (resistive and capacitive) load.

  16. Comparison of Opa Locka Tower with other ATC facilities by means of a biochemical stress index.

    DOT National Transportation Integrated Search

    1974-12-01

    Physiological and biochemical measurements of stress in 14 Opa Locka Tower (OPF) controllers indicated that the principal stressor at that facility was the heavy volume of air traffic. Controllers responded to this stressor with a large increase in u...

  17. In-Use Evaluation of Peracetic Acid for High-Level Disinfection of Endoscopes.

    PubMed

    Chenjiao, Wu; Hongyan, Zhang; Qing, Gu; Xiaoqi, Zhong; Liying, Gu; Ying, Fang

    2016-01-01

    Many high-level disinfectants have been used for disinfection of endoscopes such as 2% glutaraldehyde (GA), 0.55% ortho-phthalaldehyde (OPA), and peracetic acid (PAA). Both GA and OPA are widely used in disinfection of endoscopes and have been previously discussed, but there is little research on the practical use of PAA as an endoscope disinfectant. An experimental model of a flexible gastrointestinal endoscope being contaminated with 9 strains of microorganism was designed. After the cleaning and disinfecting procedure was completed, we evaluated the biocidal activity (850 ppm PAA, 2% GA, and 0.55% OPA) on our flexible gastrointestinal endoscope model. We also evaluated sterilization effectiveness of PAA on other bacteria, including some antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile). The residual bacterial colony count number of the PAA-disinfected endoscope was significantly lower than that of the GA- and OPA-disinfected endoscopes. The biocidal effect and efficiency of the endoscope disinfection by PAA appeared to be better than either the GA- or OPA-disinfected endoscope. PAA has demonstrated a good sterilization effect on other bacterial species; of particular note are common antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile. The results of this study demonstrate that PAA is a fast and effective high-level disinfectant for use in the reprocessing of flexible endoscopes.

  18. Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM)-mediated Inhibitory Signaling is Regulated by Sequential Phosphorylation Mediated by Distinct Nonreceptor Tyrosine Kinases: A Case Study Involving PECAM-1

    PubMed Central

    Tourdot, Benjamin E.; Brenner, Michelle K.; Keough, Kathleen C.; Holyst, Trudy; Newman, Peter J.; Newman, Debra K.

    2013-01-01

    The activation state of many blood and vascular cells is tightly controlled by a delicate balance between receptors that contain immunoreceptor tyrosine-based activation motifs (ITAMs) and those that contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Precisely how the timing of cellular activation by ITAM-coupled receptors is regulated by ITIM-containing receptors is, however, poorly understood. Using platelet endothelial cell adhesion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of inhibitory signaling occurs via a novel, sequential process in which Src family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homology 2 domain-containing non-receptor tyrosine kinases (NRTKs). NRTKs capable of mediating the second phosphorylation event include C-terminal Src kinase (Csk) and Bruton’s tyrosine kinase (Btk). Btk and Csk function downstream of phosphatidylinositol 3-kinase (PI3K) activation during ITAM-dependent platelet activation. In ITAM-activated platelets that were treated with a PI3K inhibitor, PECAM-1 was phosphorylated but did not bind the tandem SH2 domain-containing tyrosine phosphatase SHP-2, indicating that it was not phosphorylated on its N-terminal ITIM. Csk bound to and phosphorylated PECAM-1 more efficiently than did Btk, and required its SH2 domain to perform these functions. Additionally, the phosphorylation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phosphorylation of its C-terminal ITIM, providing evidence that the ITIMs of other dual ITIM-containing receptors are also sequentially phosphorylated. On the basis of these findings, we propose that sequential ITIM phosphorylation provides a general mechanism for precise temporal control over the recruitment and activation of tandem SH2 domain-containing tyrosine phosphatases that dampen ITAM-dependent signals. PMID:23418871

  19. Social Cognitive Antecedents of Fruit and Vegetable Consumption in Truck Drivers: A Sequential Mediation Analysis.

    PubMed

    Hamilton, Kyra; Vayro, Caitlin; Schwarzer, Ralf

    2015-01-01

    To examine a mechanism by which social cognitive factors may predict fruit and vegetable consumption in long-haul truck drivers. Dietary self-efficacy, positive outcome expectancies, and intentions were assessed in 148 Australian truck drivers, and 1 week later they reported their fruit and vegetable consumption. A theory-guided sequential mediation model was specified that postulated self-efficacy and intention as mediators between outcome expectancies and behavior. The hypothesized model was confirmed. A direct effect of outcome expectancies was no longer present when mediators were included, and all indirect effects were significant, including the 2-mediator chain (β = .15; P < .05; 95% confidence interval, 0.05-0.32). Truck drivers who expected benefits from dietary change, felt confident about being capable to do so, and formed an intention were likely to report larger amounts of fruit and vegetable intake. The results suggest that the role of outcome expectancies and self-efficacy are important to consider for understanding and predicting healthy eating intentions in truck drivers. Copyright © 2015 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  20. A Developmental Perspective on Peer Rejection, Deviant Peer Affiliation, and Conduct Problems Among Youth.

    PubMed

    Chen, Diane; Drabick, Deborah A G; Burgers, Darcy E

    2015-12-01

    Peer rejection and deviant peer affiliation are linked consistently to the development and maintenance of conduct problems. Two proposed models may account for longitudinal relations among these peer processes and conduct problems: the (a) sequential mediation model, in which peer rejection in childhood and deviant peer affiliation in adolescence mediate the link between early externalizing behaviors and more serious adolescent conduct problems; and (b) parallel process model, in which peer rejection and deviant peer affiliation are considered independent processes that operate simultaneously to increment risk for conduct problems. In this review, we evaluate theoretical models and evidence for associations among conduct problems and (a) peer rejection and (b) deviant peer affiliation. We then consider support for the sequential mediation and parallel process models. Next, we propose an integrated model incorporating both the sequential mediation and parallel process models. Future research directions and implications for prevention and intervention efforts are discussed.

  1. A Developmental Perspective on Peer Rejection, Deviant Peer Affiliation, and Conduct Problems among Youth

    PubMed Central

    Chen, Diane; Drabick, Deborah A. G.; Burgers, Darcy E.

    2015-01-01

    Peer rejection and deviant peer affiliation are linked consistently to the development and maintenance of conduct problems. Two proposed models may account for longitudinal relations among these peer processes and conduct problems: the (a) sequential mediation model, in which peer rejection in childhood and deviant peer affiliation in adolescence mediate the link between early externalizing behaviors and more serious adolescent conduct problems; and (b) parallel process model, in which peer rejection and deviant peer affiliation are considered independent processes that operate simultaneously to increment risk for conduct problems. In this review, we evaluate theoretical models and evidence for associations among conduct problems and (a) peer rejection and (b) deviant peer affiliation. We then consider support for the sequential mediation and parallel process models. Next, we propose an integrated model incorporating both the sequential mediation and parallel process models. Future research directions and implications for prevention and intervention efforts are discussed. PMID:25410430

  2. 30 CFR 253.1 - What is the purpose of this part?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 253.1 What... covered offshore facilities (COFs) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U...

  3. Bistability in a hybrid optomechanical system: effect of a gain medium

    NASA Astrophysics Data System (ADS)

    Asghari Nejad, A.; Baghshahi, H. R.; Askari, H. R.

    2017-11-01

    In this paper, we investigate the optical bistability of a hybrid optomechanical system consisting of two coupled cavities: a bare optomechanical cavity (with an oscillating mirror at one end) and a traditional one. The traditional cavity is filled with an optical parametric amplifier (OPA), and an input pump laser is applied to it. The Hamiltonian of the system is written in a rotating frame. The dynamics of the system is driven by the quantum Langevin equations of motion. We demonstrate that the presence of an OPA can dramatically affect the type of stability of the optomechanical cavity. We show that it is possible to create a proper optical bistability for the optomechanical cavity by changing the gain coefficient of the OPA. Also, it is shown that changing the phase of the field driving the OPA has two different effects on the bistability region of the optomechanical cavity. Moreover, we show that by choosing a proper value for the detuning of the traditional cavity it is possible to observe a tristable behavior in the optomechanical cavity.

  4. Near-Infrared Spectroscopy of Small Protonated Water Clusters

    NASA Astrophysics Data System (ADS)

    Wagner, J. Philipp; McDonald, David C., II; McCoy, Anne B.; Duncan, Michael A.

    2017-06-01

    Small protonated water clusters and their argon tagged analogues of the general formula H^{+}(H_{2}O)_{n}Ar_{m} have been generated in a pulsed electric discharge source. Clusters containing n=1-8 water molecules were mass-selected and their absorptions in the near-infrared were probed with a tunable Nd/colonYAG pumped OPA/OPA laser system in the region from 4850-7350 cm^{-1}. A doublet corresponding to overtones of the free O-H stretches of the external waters was observed around 7200 cm^{-1} that was continuously decreasing in intensity with increasing cluster size. Broad, mostly featureless absorptions were found around 5300 cm^{-1} associated with stretch/bend combinations and with the hydrogen bonded waters in the core of the clusters. Vibrational assignments were substantiated by comparison to anharmonic frequency computations via second-order vibrational perturbation theory (VPT2) at the MP2/aug-cc-pVTZ level of theory.

  5. Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E2, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

    PubMed Central

    Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong

    2010-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods. PMID:20808670

  6. Efficacy of dendritic cells matured early with OK-432 (Picibanil), prostaglandin E2, and interferon-alpha as a vaccine for a hormone refractory prostate cancer cell line.

    PubMed

    Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong; Kim, Choung-Soo

    2010-09-01

    Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

  7. Correlation between ocular pulse amplitude measured by dynamic contour tonometer and colour Doppler flow imaging of the arteric retrobulbar vessels.

    PubMed

    Marjanović, Ivan; Mijajlović, Milija; Covicković-Sternić, Nadezda; Kontić, Djordje; Hentova-Senćanić, Paraskeva; Marković, Vujica; Bozić, Marija

    2011-01-01

    An altered perfusion of the optic nerve head has been proposed as a pathogenic factor in glaucoma. The aim of this study was to evaluate the correlation between ocular pulse amplitude (OPA), measured by Dynamic contour tonometer (DCT) and colour Doppler imaging (CDI) of the arteric retrobulbar vessels. Twenty patients older than 50 years were examined, and divided into two equal groups. The first group comprised of patients with normal tension glaucoma treated with topical antiglaucomatous therapy, and the second group included patients with ocular hypertension and glaucoma suspicious without any antiglaucomatous therapy. Ocular pulse amplitude (OPA) was measured with DCT. CDI was also performed. We measured haemodynamic parameters of the internal carotid artery (ICA), ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCA). Peak systolic (PSV), end-diastolic (EDV) velocities were measured, and resistance index (RI) and pulsatility index (PI) were calculated. Correlation with OPA showed indirect servitude in the RI of the ICA, RI and PI of the CRA, in the first group; and in the PSV and EDV of the ICA, in the RI and PI of the OA, EDV and RI of the CRA, and RI of the PCA, in the second group Increase of OPA was mostly followed by the increase of the parameters (PSV, EDV, RI, and PI) of the arteric retrobulbar vessels in the first group; in the second group, increase of OPA was in almost 50% of parameters followed by their decrease.

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

    Park, Jeehye; Lee, Gina; Chung, Jongkyeong

    The two Parkinson's disease (PD) genes, PTEN-induced kinase 1 (PINK1) and parkin, are linked in a common pathway which affects mitochondrial integrity and function. However, it is still not known what this pathway does in the mitochondria. Therefore, we investigated its physiological function in Drosophila. Because Drosophila PINK1 and parkin mutants show changes in mitochondrial morphology in both indirect flight muscles and dopaminergic neurons, we here investigated whether the PINK1-Parkin pathway genetically interacts with the regulators of mitochondrial fusion and fission such as Drp1, which promotes mitochondrial fission, and Opa1 or Marf, which induces mitochondrial fusion. Surprisingly, DrosophilaPINK1 and parkinmore » mutant phenotypes were markedly suppressed by overexpression of Drp1 or downregulation of Opa1 or Marf, indicating that the PINK1-Parkin pathway regulates mitochondrial remodeling process in the direction of promoting mitochondrial fission. Therefore, we strongly suggest that mitochondrial fusion and fission process could be a prominent therapeutic target for the treatment of PD.« less

  9. Computational mechanisms underlying cortical responses to the affordance properties of visual scenes

    PubMed Central

    Epstein, Russell A.

    2018-01-01

    Biologically inspired deep convolutional neural networks (CNNs), trained for computer vision tasks, have been found to predict cortical responses with remarkable accuracy. However, the internal operations of these models remain poorly understood, and the factors that account for their success are unknown. Here we develop a set of techniques for using CNNs to gain insights into the computational mechanisms underlying cortical responses. We focused on responses in the occipital place area (OPA), a scene-selective region of dorsal occipitoparietal cortex. In a previous study, we showed that fMRI activation patterns in the OPA contain information about the navigational affordances of scenes; that is, information about where one can and cannot move within the immediate environment. We hypothesized that this affordance information could be extracted using a set of purely feedforward computations. To test this idea, we examined a deep CNN with a feedforward architecture that had been previously trained for scene classification. We found that responses in the CNN to scene images were highly predictive of fMRI responses in the OPA. Moreover the CNN accounted for the portion of OPA variance relating to the navigational affordances of scenes. The CNN could thus serve as an image-computable candidate model of affordance-related responses in the OPA. We then ran a series of in silico experiments on this model to gain insights into its internal operations. These analyses showed that the computation of affordance-related features relied heavily on visual information at high-spatial frequencies and cardinal orientations, both of which have previously been identified as low-level stimulus preferences of scene-selective visual cortex. These computations also exhibited a strong preference for information in the lower visual field, which is consistent with known retinotopic biases in the OPA. Visualizations of feature selectivity within the CNN suggested that affordance-based responses encoded features that define the layout of the spatial environment, such as boundary-defining junctions and large extended surfaces. Together, these results map the sensory functions of the OPA onto a fully quantitative model that provides insights into its visual computations. More broadly, they advance integrative techniques for understanding visual cortex across multiple level of analysis: from the identification of cortical sensory functions to the modeling of their underlying algorithms. PMID:29684011

  10. 76 FR 59731 - Draft Damage Assessment and Restoration Plan and Environmental Assessment for the M/V Cosco Busan...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-27

    ... for restoring injured natural resources and compensating recreational losses resulting from the Cosco... under OPA, will pay damages to compensate the public for the injuries to natural resources and lost... accordance with the OPA, the Natural Resource Damage Assessment regulations found in the Code of Federal...

  11. Fault Frictional Stability in a Nuclear Waste Repository

    NASA Astrophysics Data System (ADS)

    Orellana, Felipe; Violay, Marie; Scuderi, Marco; Collettini, Cristiano

    2016-04-01

    Exploitation of underground resources induces hydro-mechanical and chemical perturbations in the rock mass. In response to such disturbances, seismic events might occur, affecting the safety of the whole engineering system. The Mont Terri Rock Laboratory is an underground infrastructure devoted to the study of geological disposal of nuclear waste in Switzerland. At the site, it is intersected by large fault zones of about 0.8 - 3 m in thickness and the host rock formation is a shale rock named Opalinus Clay (OPA). The mineralogy of OPA includes a high content of phyllosilicates (50%), quartz (25%), calcite (15%), and smaller proportions of siderite and pyrite. OPA is a stiff, low permeable rock (2×10-18 m2), and its mechanical behaviour is strongly affected by the anisotropy induced by bedding planes. The evaluation of fault stability and associated fault slip behaviour (i.e. seismic vs. aseismic) is a major issue in order to ensure the long-term safety and operation of the repository. Consequently, experiments devoted to understand the frictional behaviour of OPA have been performed in the biaxial apparatus "BRAVA", recently developed at INGV. Simulated fault gouge obtained from intact OPA samples, were deformed at different normal stresses (from 4 to 30 MPa), under dry and fluid-saturated conditions. To estimate the frictional stability, the velocity-dependence of friction was evaluated during velocity steps tests (1-300 μm/s). Slide-hold-slide tests were performed (1-3000 s) to measure the amount of frictional healing. The collected data were subsequently modelled with the Ruina's slip dependent formulation of the rate and state friction constitutive equations. To understand the deformation mechanism, the microstructures of the sheared gouge were analysed. At 7 MPa normal stress and under dry conditions, the friction coefficient decreased from a peak value of μpeak,dry = 0.57 to μss,dry = 0.50. Under fluid-saturated conditions and same normal stress, the friction coefficient decreased from a peak value of μpeak,sat = 0.45 to μss,sat = 0.34. Additionally, it has been observed that the weakening distance Dw is smaller under fluid- saturated conditions (˜4 mm) compared to dry conditions (˜6 mm). Results showed a linear decrease of both peak friction and steady state friction when normal stress increases. When fluid- saturation degree of gouges is reduced, gouge samples underwent a transition from velocity strengthening to velocity weakening behaviour, thus indicating a potentially unstable frictional behaviour of the fault. Furthermore, under both saturated and dry conditions, the frictional healing rate showed a low recovery of the friction coefficient under different holding times. Our experiments indicate that the frictional behaviour of Opalinus Clay is characterized by complex processes depending upon normal stress, sliding velocity, and saturation degree of the samples. This complexity highlights the need for further experiments in order to better evaluate the seismic risk during long-term nuclear waste disposal within the OPA clay formation.

  12. Demonstration of a 100-mJ OPO/OPA for future lidar applications and laser-induced damage threshold testing of optical components for MERLIN

    NASA Astrophysics Data System (ADS)

    Elsen, Florian; Livrozet, Marie; Strotkamp, Michael; Wüppen, Jochen; Jungbluth, Bernd; Kasemann, Raphael; Löhring, Jens; Meissner, Ansgar; Meyer, Rudolf; Hoffmann, Hans-Dieter; Poprawe, Reinhart

    2018-02-01

    In the field of atmospheric research, lidar is a powerful technology that can measure gas or aerosol concentrations, wind speed, or temperature profiles remotely. To conduct such measurements globally, spaceborne systems are advantageous. Pulse energies in the 100-mJ range are required to achieve highly accurate, longitudinal resolved measurements. Measuring concentrations of specific gases, such as CH4 or CO2, requires output wavelengths in the IR-B, which can be addressed by optical-parametric frequency conversion. An OPO/OPA frequency conversion setup was designed and built as a demonstration module to address the 1.6-μm range. The pump laser is an Nd:YAG-MOPA system, consisting of a stable oscillator and two subsequent Innoslab-based amplifier stages that deliver up to 500 mJ of output pulse energy at 100 Hz repetition frequency. The OPO is inherited from the OPO design for the CH4 lidar instrument on the French-German climate satellite methane remote-sensing lidar mission (MERLIN). To address the 100-mJ regime, the OPO output beam is amplified in a subsequent multistage OPA. With potassium titanyl phosphate as nonlinear medium, the OPO/OPA delivered more than 100 mJ of output energy at 1645 nm from 450 mJ of the pump energy and a pump pulse duration of 30 ns. This corresponds to a quantum conversion efficiency of about 25%. In addition to demonstrating optical performance for future lidar systems, this laser will be part of a laser-induced damage thresholds test facility, which will be used to qualify optical components especially for the MERLIN.

  13. Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa

    PubMed Central

    Muenzner, Petra; Kengmo Tchoupa, Arnaud; Klauser, Benedikt; Brunner, Thomas; Putze, Johannes; Dobrindt, Ulrich; Hauck, Christof R.

    2016-01-01

    Attachment to the host mucosa is a key step in bacterial pathogenesis. On the apical surface of epithelial cells, members of the human carcinoembryonic antigen (CEA) family are abundant glycoproteins involved in cell-cell adhesion and modulation of cell signaling. Interestingly, several gram-negative bacterial pathogens target these receptors by specialized adhesins. The prototype of a CEACAM-binding pathogen, Neisseria gonorrhoeae, utilizes colony opacity associated (Opa) proteins to engage CEA, as well as the CEA-related cell adhesion molecules CEACAM1 and CEACAM6 on human epithelial cells. By heterologous expression of neisserial Opa proteins in non-pathogenic E. coli we find that the Opa protein-CEA interaction is sufficient to alter gene expression, to increase integrin activity and to promote matrix adhesion of infected cervical carcinoma cells and immortalized vaginal epithelial cells in vitro. These CEA-triggered events translate in suppression of exfoliation and improved colonization of the urogenital tract by Opa protein-expressing E. coli in CEA-transgenic compared to wildtype mice. Interestingly, uropathogenic E. coli expressing an unrelated CEACAM-binding protein of the Afa/Dr adhesin family recapitulate the in vitro and in vivo phenotype. In contrast, an isogenic strain lacking the CEACAM-binding adhesin shows reduced colonization and does not suppress epithelial exfoliation. These results demonstrate that engagement of human CEACAMs by distinct bacterial adhesins is sufficient to blunt exfoliation and to promote host infection. Our findings provide novel insight into mucosal colonization by a common UPEC pathotype and help to explain why human CEACAMs are a preferred epithelial target structure for diverse gram-negative bacteria to establish a foothold on the human mucosa. PMID:27171273

  14. Generic method for the absolute quantification of glutathione S-conjugates: Application to the conjugates of acetaminophen, clozapine and diclofenac.

    PubMed

    den Braver, Michiel W; Vermeulen, Nico P E; Commandeur, Jan N M

    2017-03-01

    Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione (GSH). Although sensitivity of modern mass spectrometrical methods is extremely high, absolute quantification of GSH-conjugates is critically dependent on the availability of authentic references. Although 1 H NMR is currently the method of choice for quantification of metabolites formed biosynthetically, its intrinsically low sensitivity can be a limiting factor in quantification of GSH-conjugates which generally are formed at low levels. In the present study, a simple but sensitive and generic method for absolute quantification of GSH-conjugates is presented. The method is based on quantitative alkaline hydrolysis of GSH-conjugates and subsequent quantification of glutamic acid and glycine by HPLC after precolumn derivatization with o-phthaldialdehyde/N-acetylcysteine (OPA/NAC). Because of the lower stability of the glycine OPA/NAC-derivate, quantification of the glutamic acid OPA/NAC-derivate appeared most suitable for quantification of GSH-conjugates. The novel method was used to quantify the concentrations of GSH-conjugates of diclofenac, clozapine and acetaminophen and quantification was consistent with 1 H NMR, but with a more than 100-fold lower detection limit for absolute quantification. Copyright © 2017. Published by Elsevier B.V.

  15. 2017 Military Investigation and Justice Experience Survey: Overview Report

    DTIC Science & Technology

    2018-04-30

    2016–2017 Military Investigation and Justice Experience Survey (MIJES) Overview Report Additional copies of this report may be obtained...www.dtic.mil/dtic/order.html OPA Report No. 2017-027 January 2018 2016–2017 Military Investigation and Justice Experience Survey (MIJES...Investigation and Justice Experience Survey (MIJES) ii Acknowledgments Acknowledgments The Office of People Analytics (OPA) is indebted to numerous

  16. 2017 Workplace and Gender Relations Survey of Reserve Component Members: Statistical Methodology Report

    DTIC Science & Technology

    2018-04-30

    2017 Workplace and Gender Relations Survey of Reserve Component Members Statistical Methodology Report Additional copies of this report...Survey of Reserve Component Members Statistical Methodology Report Office of People Analytics (OPA) 4800 Mark Center Drive, Suite...RESERVE COMPONENT MEMBERS STATISTICAL METHODOLOGY REPORT Introduction The Office of People Analytics’ Center for Health and Resilience (OPA[H&R

  17. 78 FR 46339 - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of Temporary Moratoria...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ...-crm-510.html . \\10\\ Department of Justice, ``Owners of Miami Home Health Companies Sentenced to Prison in $48 million Health Care Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/February/13-crm-243... Convicted in Medicare Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/March/13-crm-273.html . \\24...

  18. 13.5 nm High Harmonic Generation Driven by a Visible Noncollinear Optical Parametric Amplifier

    DTIC Science & Technology

    2011-11-11

    compressed through a CaF2 prism pair at Brewster angle , and directed to the second OPA stage after a periscope flipping its polarization. The 90% part of...FWHM pulse duration. HHG setup The OPA pulses are sent into a vacuum chamber and focused in an Argon ( lens focal length 150 mm) or Helium (focal

  19. The Causes of Blistering in Boat Building Materials

    DTIC Science & Technology

    1986-08-01

    acrylate units (MET) Ethylene glycol (MET) Propylene glycol (MET) Neopentyl glycol (NET) Maleic acid or anhydride (unsaturated) (NET) lumaric acid...PROPYLENE GLYCOL OPA ORTHOPHTHALIC ACID VINYL - URETHANE BASED POLYESTER IqPG NEOPENTYL GLYCOL RESIN EG - ETHYLENE GLYCOL TMPD - 22,, - TRiMETHY...IPA Isophthalic acid WSN Low molecular weight water soluble material NPG Neopentyl glycol OPA Orthophthalio acid PG Propylene glycol MEKP Hethyl

  20. Phonon-assisted nonlinear optical processes in ultrashort-pulse pumped optical parametric amplifiers

    NASA Astrophysics Data System (ADS)

    Isaienko, Oleksandr; Robel, István

    2016-03-01

    Optically active phonon modes in ferroelectrics such as potassium titanyl phosphate (KTP) and potassium titanyl arsenate (KTA) in the ~7-20 THz range play an important role in applications of these materials in Raman lasing and terahertz wave generation. Previous studies with picosecond pulse excitation demonstrated that the interaction of pump pulses with phonons can lead to efficient stimulated Raman scattering (SRS) accompanying optical parametric oscillation or amplification processes (OPO/OPA), and to efficient polariton-phonon scattering. In this work, we investigate the behavior of infrared OPAs employing KTP or KTA crystals when pumped with ~800-nm ultrashort pulses of duration comparable to the oscillation period of the optical phonons. We demonstrate that under conditions of coherent impulsive Raman excitation of the phonons, when the effective χ(2) nonlinearity cannot be considered instantaneous, the parametrically amplified waves (most notably, signal) undergo significant spectral modulations leading to an overall redshift of the OPA output. The pump intensity dependence of the redshifted OPA output, the temporal evolution of the parametric gain, as well as the pump spectral modulations suggest the presence of coupling between the nonlinear optical polarizations PNL of the impulsively excited phonons and those of parametrically amplified waves.

  1. Dispersing surface-modified imogolite nanotubes in polar and non-polar solvents

    NASA Astrophysics Data System (ADS)

    Li, Ming; Brant, Jonathan A.

    2018-02-01

    Furthering the development of nanocomposite structures, namely membranes for water treatment applications, requires that methods be developed to ensure nanoparticle dispersion in polar and non-polar solvents, as both are widely used in associated synthesis techniques. Here, we report on a two-step method to graft polyvinylpyrrolidone (PVP), and a one-step method for octadecylphosphonic acid (OPA), onto the outer surfaces of imogolite nanotubes. The goal of these approaches was to improve and maintain nanotube dispersion in polymer compatible polar and non-polar solvents. The PVP coating modified the imogolite surface charge from positive to weakly negative at pH ≤ 9; the OPA made it weakly positive at acidic pH values to negative at pH ≥ 7. The PVP surface coating stabilized the nanotubes through steric hindrance in polar protic, dipolar aprotic, and chloroform. In difference to the PVP, the OPA surface coating allowed the nanotubes to be dispersed in n-hexane and chloroform, but not in the polar solvents. The lack of miscibility in the polar solvents, as well as the better dispersion in n-hexane, was attributed to the stronger hydrophobicity of the OPA polymer relative to the PVP. [Figure not available: see fulltext.

  2. Fluorometric enzymatic assay of L-arginine

    NASA Astrophysics Data System (ADS)

    Stasyuk, Nataliya; Gayda, Galina; Yepremyan, Hasmik; Stepien, Agnieszka; Gonchar, Mykhailo

    2017-01-01

    The enzymes of L-arginine (further - Arg) metabolism are promising tools for elaboration of selective methods for quantitative Arg analysis. In our study we propose an enzymatic method for Arg assay based on fluorometric monitoring of ammonia, a final product of Arg splitting by human liver arginase I (further - arginase), isolated from the recombinant yeast strain, and commercial urease. The selective analysis of ammonia (at 415 nm under excitation at 360 nm) is based on reaction with o-phthalaldehyde (OPA) in the presence of sulfite in alkali medium: these conditions permit to avoid the reaction of OPA with any amino acid. A linearity range of the fluorometric arginase-urease-OPA method is from 100 nM to 6 μМ with a limit of detection of 34 nM Arg. The method was used for the quantitative determination of Arg in the pooled sample of blood serum. The obtained results proved to be in a good correlation with the reference enzymatic method and literature data. The proposed arginase-urease-OPA method being sensitive, economical, selective and suitable for both routine and micro-volume formats, can be used in clinical diagnostics for the simultaneous determination of Arg as well as urea and ammonia in serum samples.

  3. Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

    PubMed

    Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

    2017-09-07

    Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Igor V. Litvinyuk, and Itzik Ben-Itzhak

    Our principal goal was the experimental demonstration of Laser-Induced Electron Diffraction (LIED). Key steps along the development of this experimental technique have been accomplished and reported in the publications listed in this brief report. We started with measuring 3D electron momenta spectra in aligned nitrogen and oxygen molecules. Chakra Maharjan (Ph.D. student of Lew Cocke) was a lead researcher on this project. Although Chakra succeeded in obtaining those spectra, we were scooped by the publication of identical results in Science by the NRC Ottawa group. Our results were never published as a refereed article, but became a part of Chakra'smore » Ph.D. dissertation. That Science paper was the first experimental demonstration of Laser-Induced Electron Diffraction (LIED). Chakra also worked on wavelength dependence of 3D ATI spectra of atoms and molecules using tunable OPA pulses. Another Ph.D. student, Maia Magrakvelidze (her GRA was funded by the grant), started working on COLTRIMS experiments using OPA pulses (1800 nm wavelength). After some initial experiments it became apparent that COLTRIMS did not yield sufficient count rates of electrons in the high-energy part of the spectrum to see diffraction signatures with acceptable statistics (unfavorable scaling of the electron yield with laser wavelength was partly to blame). Nevertheless, Maia managed to use COLTRIMS and OPA to measure the angular dependence of the tunneling ionization rate in D{sub 2} molecules. Following the initial trial experiments, the decision was made to switch from COLTRIMS to VMI in order to increase the count rates by a factor of {approx}100, which may have given us a chance to see LIED. Research Associate Dr. Sankar De (his salary was funded by the grant), in collaboration with Matthias Kling's group (then at MPQ Garching), proceeded to design a special multi-electrode VMI spectrometer for capturing high-energy ATI electrons and to install it in place of COLTRIMS inside our experimental chamber. That apparatus was later used for the first demonstration of field-free orientation in CO using two-color laser pulses as well as for a series of other experiments, such as pump-probe studies of molecular dynamics with few-cycle laser pulses, control of electron localization in dissociating hydrogen molecules using two-color laser pulses, and ATI spectra of Xe ionized by two-color laser pulses. In parallel, Dipanwita Ray (Ph.D. student of Lew Cocke) worked on measuring angle-resolved ATI spectra of noble gases using a stereo-ATI phasemeter as a TOF electron spectrometer. She observed the angular diffraction structures in 3D ATI spectra of Ar, Kr and Xe, which were interpreted in terms of the Quantitative Rescattering theory newly developed by C.D. Lin. We also attempted to use a much more powerful OPA (five times more energy per pulse than the one we had at JRML) available at the Advanced Laser Light Source (ALLS) in Montreal to observe LIED. Two visits to ALLS by the PI, Igor Litvinyuk, and one visit by the PI's Ph.D. student (Irina Bocharova) were funded by the grant. Though we failed to observe LIED (the repetition rate of the ALLS OPA was too low at only 100 Hz), this international collaboration resulted in several publications on other related subjects, such as the wavelength dependence of laser Coulomb explosion of hydrogen, the wavelength dependence of non-sequential double ionization of neon and argon, the demonstration of charge-resonance enhanced ionization in CO{sub 2}, and the study of non-elastic scattering processes in H{sub 2}. Theoretical efforts to account for the hydrogen Coulomb explosion experiment resulted in another paper by Maia Magrakvelidze as lead author. Although for various reasons we failed to achieve our main goal of observing LIED, we salute the recent success in this endeavor by Lou DiMauro's group (with theoretical support from our KSU colleague C.D. Lin) published in Nature, which validates our approach.« less

  5. Leisure-Time and Occupational Physical Activity in Early and Late Adulthood in Relation to Later Life Physical Functioning.

    PubMed

    Kulmala, Jenni; Ngandu, Tiia; Pajala, Satu; Lehtisalo, Jenni; Levälahti, Esko; Antikainen, Riitta; Laatikainen, Tiina; Oksa, Heikki; Peltonen, Markku; Rauramaa, Rainer; Soininen, Hilkka; Strandberg, Timo; Tuomilehto, Jaakko; Kivipelto, Miia

    2016-10-01

    Physical activity (PA) has beneficial effects on older age physical functioning, but longitudinal studies with follow-ups extending up to decades are few. We investigated the association between leisure-time PA (LTPA) and occupational PA (OPA) from early to late adulthood in relation to later life performance-based physical functioning. The study involved 1260 people aged 60 to 79 years who took part in assessments of physical functioning (Short Physical Performance Battery [SPPB] test, 10-m maximal walking test, and grip strength test). Participants' data on earlier life LTPA/OPA (age range 25 to 74 years) were received from the previous studies (average follow-up 13.4 years). Logistic, linear, and censored regression models were used to assess the associations between LTPA/OPA earlier in life and subsequent physical functioning. A high level of LTPA earlier in life was associated with a lower risk of having difficulties on the SPPB test (odds ratio [OR]: 0.37; 95% confidence interval [CI], 0.24-0.58) and especially on the chair rise test (OR: 0.42; 95% CI, 0.27-0.64) in old age. Heavy manual work predicted difficulties on SPPB (OR: 1.91; 95% CI, 1.22-2.98) and the chair rise test (OR: 1.75; 95% CI, 1.14-2.69) and poorer walking speed (β = .10, P = .005). This study highlights the importance of LTPA on later life functioning, but also indicates the inverse effects that may be caused by heavy manual work.

  6. Project-Based Learning with an Online Peer Assessment System in a Photonics Instruction for Enhancing LED Design Skills

    ERIC Educational Resources Information Center

    Chang, Shu-Hsuan; Wu, Tsung-Chih; Kuo, Yen-Kuang; You, Li-Chih

    2012-01-01

    This study proposed a novel instructional approach, a two-stage LED simulation of Project-based learning (PBL) course with online peer assessment (OPA), and explored how to apply OPA to the different structured problems in a PBL course to enhance students' professional skills in LED design as well as meta-cognitive thinking. The participants of…

  7. Improved Performance of an Optically Pumped Mid-Infrared Acetylene-Filled Hollow-Core Fiber Laser

    NASA Astrophysics Data System (ADS)

    Dadashzadeh, Neda

    The focus of this research is improving the pulse output energy of a mid-IR pulsed acetylene-filled Hollow-core Optical Fiber Gas LASer (HOFGLAS) system. Pump pulses and acetylene molecules interact with each other inside hollow-core photonic crystal fiber that effectively confines light and allows for strong gain. This results in lasing at 3.11 mum and 3.17 mum lines based on population inversion of acetylene molecules, which are optically pumped at rotational-vibrational overtones near 1.5 mum using 1 ns pulse duration from an optical parametric amplifier (OPA). This acetylene laser operates with no cavity mirrors because of a high gain in a single pass configuration. There are few laser sources in the mid-IR region while there are many applications for having a laser source in this range such as remote sensing, hazardous chemical detection, and breath analysis. This adds to the importance of the acetylene-filled HOFGLAS system. Some of the applications like remote sensing require high power. So, we moved toward power scaling this laser system by optimizing the laser operation through maximizing the OPA alignment to improve its modal content using longer length of fiber to increase the interaction length and improving the beam quality of the mid-IR emissions. The highest pulse energy ever obtained in the 3 microm mid-IR region from the acetylene-filled HOFGLAS after applying the improvements is reported here (1.4 muJ). Higher mid-IR pulse energies can be achieved by improving the pulse energy achievable from the OPA pump source and working with longer pulse duration to decrease the bandwidth of the OPA. This operation demonstrates many novel properties of acetylene-filled pulsed mid-IR hollow-core fiber lasers. The excellent spatial beam quality at highest power and phenomenological scaling of saturation power and efficiency with pressure that we observe point to the promise of power scaling and motivate further development of numerical models of the laser for deeper insight into these effects. M2 measurement method was used to examine spatial beam quality and it was found to be fiber-dependent. For the improved setup, M2 was investigated at several input pump powers in addition to the reproducibility checks. M 2 of 1.14 at the maximum output power motivates for beam combining to scale to higher power. The independence of efficiency on pressure is an evidence for reaching higher mid-IR power at a pressure where saturation behavior does not exist. achieving the highest mid-IR power to date, 1.4 muJ, encourages for building higher power OPA to produce high power mid-IR emissions. Taken as a whole, this laser exhibits novel behavior that motivates both numerical/theoretical investigation and further efforts to scale to higher powers.

  8. High repetition rate tunable femtosecond pulses and broadband amplification from fiber laser pumped parametric amplifier.

    PubMed

    Andersen, T V; Schmidt, O; Bruchmann, C; Limpert, J; Aguergaray, C; Cormier, E; Tünnermann, A

    2006-05-29

    We report on the generation of high energy femtosecond pulses at 1 MHz repetition rate from a fiber laser pumped optical parametric amplifier (OPA). Nonlinear bandwidth enhancement in fibers provides the intrinsically synchronized signal for the parametric amplifier. We demonstrate large tunability extending from 700 nm to 1500 nm of femtosecond pulses with pulse energies as high as 1.2 muJ when the OPA is seeded by a supercontinuum generated in a photonic crystal fiber. Broadband amplification over more than 85 nm is achieved at a fixed wavelength. Subsequent compression in a prism sequence resulted in 46 fs pulses. With an average power of 0.5 W these pulses have a peak-power above 10 MW. In particular, the average power and pulse energy scalability of both involved concepts, the fiber laser and the parametric amplifier, will enable easy up-scaling to higher powers.

  9. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

    The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,…

  10. Atypical mitochondrial fission upon bacterial infection

    PubMed Central

    Stavru, Fabrizia; Palmer, Amy E.; Wang, Chunxin; Youle, Richard J.; Cossart, Pascale

    2013-01-01

    We recently showed that infection by Listeria monocytogenes causes mitochondrial network fragmentation through the secreted pore-forming toxin listeriolysin O (LLO). Here, we examine factors involved in canonical fusion and fission. Strikingly, LLO-induced mitochondrial fragmentation does not require the traditional fission machinery, as Drp1 oligomers are absent from fragmented mitochondria following Listeria infection or LLO treatment, as the dynamin-like protein 1 (Drp1) receptor Mff is rapidly degraded, and as fragmentation proceeds efficiently in cells with impaired Drp1 function. LLO does not cause processing of the fusion protein optic atrophy protein 1 (Opa1), despite inducing a decrease in the mitochondrial membrane potential, suggesting a unique Drp1- and Opa1-independent fission mechanism distinct from that triggered by uncouplers or the apoptosis inducer staurosporine. We show that the ER marks LLO-induced mitochondrial fragmentation sites even in the absence of functional Drp1, demonstrating that the ER activity in regulating mitochondrial fission can be induced by exogenous agents and that the ER appears to regulate fission by a mechanism independent of the canonical mitochondrial fission machinery. PMID:24043775

  11. Offset-Free Gigahertz Midinfrared Frequency Comb Based on Optical Parametric Amplification in a Periodically Poled Lithium Niobate Waveguide

    NASA Astrophysics Data System (ADS)

    Mayer, A. S.; Phillips, C. R.; Langrock, C.; Klenner, A.; Johnson, A. R.; Luke, K.; Okawachi, Y.; Lipson, M.; Gaeta, A. L.; Fejer, M. M.; Keller, U.

    2016-11-01

    We report the generation of an optical-frequency comb in the midinfrared region with 1-GHz comb-line spacing and no offset with respect to absolute-zero frequency. This comb is tunable from 2.5 to 4.2 μ m and covers a critical spectral region for important environmental and industrial applications, such as molecular spectroscopy of trace gases. We obtain such a comb using a highly efficient frequency conversion of a near-infrared frequency comb. The latter is based on a compact diode-pumped semiconductor saturable absorber mirror-mode-locked ytterbium-doped calcium-aluminum gadolynate (Yb:CALGO) laser operating at 1 μ m . The frequency-conversion process is based on optical parametric amplification (OPA) in a periodically poled lithium niobate (PPLN) chip containing buried waveguides fabricated by reverse proton exchange. The laser with a repetition rate of 1 GHz is the only active element of the system. It provides the pump pulses for the OPA process as well as seed photons in the range of 1.4 - 1.8 μ m via supercontinuum generation in a silicon-nitride (Si3 N4 ) waveguide. Both the PPLN and Si3 N4 waveguides represent particularly suitable platforms for low-energy nonlinear interactions; they allow for mid-IR comb powers per comb line at the microwatt level and signal amplification levels up to 35 dB, with 2 orders of magnitude less pulse energy than reported in OPA systems using bulk devices. Based on numerical simulations, we explain how high amplification can be achieved at low energy using the interplay between mode confinement and a favorable group-velocity mismatch configuration where the mid-IR pulse moves at the same velocity as the pump.

  12. Theoretical investigation on ratiometric two-photon fluorescent probe for Zn2+ detection based on ICT mechanism

    NASA Astrophysics Data System (ADS)

    Huang, Shuang; Yang, Bao-Zhu; Ren, Ai-Min

    2016-06-01

    OPA (one-photon absorption), TPA (two-photon absorption) and fluorescence properties of a free ligand L upon coordination with Zn2+, and the regeneration with CN- were investigated in theory. According to our research, OPA spectra of ligand L show red-shift binding with Zn2+ while blue-shift with CN-. The fluorescence spectra and TPA wavelength are shifted in the same situation as those of OPA spectra. The value of TPA cross-section decreased at first, and then increased to 1813 GM for [L-Zn(CN)4]2-. Intramolecular charge transfer (ICT) mechanism was investigated by natural bond orbital (NBO) analysis. It demonstrates that L is hopeful to be a good ratiometric fluorescent probe for zinc ion detection in solution, and it can regenerate after CN- was introduced.

  13. Interrole conflict and self-efficacy to manage work and family demands mediate the relationships of job and family demands with stress in the job and family domains.

    PubMed

    Smoktunowicz, Ewelina; Cieslak, Roman; Demerouti, Evangelia

    2017-09-01

    This study derives from Work-Home Resources model (ten Brummelhuis, L. L., & Bakker, A. B. (2012). A resource perspective on the work-home interface: The work-home resources model. American Psychologist, 67(7), 545-556. doi: 10.1037/a0027974 ) and Social Cognitive Theory (Bandura, A. (1986). Social foundations of thought and action: A social cognitive theory. Englewood Cliffs, NJ, US: Prentice-Hall, Inc.) to investigate mechanisms responsible for the effect of job and family demands on work- and family-related perceived stress. We hypothesized that interrole conflict and self-efficacy to manage work and family demands operate either independently or sequentially transmitting the effects of demands on perceived stress. A sample of 100 employees of various occupations participated in the study conducted online in two waves: Time 1 (T1) and Time 2 (T2) with a three-month interval. Regression analysis with bootstrapping was applied. Interrole conflict (T1) did not mediate the relationships between demands (T1) and perceived stress (T2), whereas self-efficacy (T1) mediated only those between family demands (T1) and stress (T2). However, data supported the sequential mediation hypotheses: Demands (T1) were associated with increased interrole conflict (T1) which in turn decreased self-efficacy (T1) and ultimately resulted in the elevated perceived stress at work and in the family (T2). Demands originating in one domain can impact stress both in the same and other life areas through the sequence of interrole conflict and context-specific self-efficacy.

  14. The relationship between internalized stigma and quality of life among people with mental illness: are self-esteem and sense of coherence sequential mediators?

    PubMed

    Świtaj, Piotr; Grygiel, Paweł; Chrostek, Anna; Nowak, Izabela; Wciórka, Jacek; Anczewska, Marta

    2017-09-01

    To elucidate the mechanism through which internalized stigma reduces the quality of life (QoL) of people with mental illness by exploring the mediating roles of self-esteem and sense of coherence (SOC). A cross-sectional analysis of 229 patients diagnosed with schizophrenia or affective disorders was undertaken to test a sequential mediation model assuming that more severe internalized stigma is related to lower self-esteem, which is associated with weaker SOC, which in turn relates to worse QoL. The proposed model was supported by the data. A sequential indirect effect from internalized stigma to QoL via self-esteem and SOC turned out to be significant [beta = -0.06, SE = 0.02; 95% CI (-0.11, -0.03)]. Support was also found for simple mediation models with either self-esteem or SOC as single mediators between internalized stigma and QoL. Self-esteem and SOC are personal resources that should be considered as potential targets of interventions aiming to prevent the harmful consequences of internalized stigma for the QoL of people receiving psychiatric treatment.

  15. Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.

    PubMed

    Rocca, Maria A; Bianchi-Marzoli, Stefania; Messina, Roberta; Cascavilla, Maria Lucia; Zeviani, Massimo; Lamperti, Costanza; Milesi, Jacopo; Carta, Arturo; Cammarata, Gabriella; Leocani, Letizia; Lamantea, Eleonora; Bandello, Francesco; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

    2015-05-01

    Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

  16. Phonon-assisted nonlinear optical processes in ultrashort-pulse pumped optical parametric amplifiers

    DOE PAGES

    Isaienko, Oleksandr; Robel, Istvan

    2016-03-15

    Optically active phonon modes in ferroelectrics such as potassium titanyl phosphate (KTP) and potassium titanyl arsenate (KTA) in the ~7–20 THz range play an important role in applications of these materials in Raman lasing and terahertz wave generation. Previous studies with picosecond pulse excitation demonstrated that the interaction of pump pulses with phonons can lead to efficient stimulated Raman scattering (SRS) accompanying optical parametric oscillation or amplification processes (OPO/OPA), and to efficient polariton-phonon scattering. In this work, we investigate the behavior of infrared OPAs employing KTP or KTA crystals when pumped with ~800-nm ultrashort pulses of duration comparable to themore » oscillation period of the optical phonons. We demonstrate that under conditions of coherent impulsive Raman excitation of the phonons, when the effective χ (2) nonlinearity cannot be considered instantaneous, the parametrically amplified waves (most notably, signal) undergo significant spectral modulations leading to an overall redshift of the OPA output. Furthermore, the pump intensity dependence of the redshifted OPA output, the temporal evolution of the parametric gain, as well as the pump spectral modulations suggest the presence of coupling between the nonlinear optical polarizations P NL of the impulsively excited phonons and those of parametrically amplified waves.« less

  17. Time trends in physical activity from 1982 to 2012 in Finland.

    PubMed

    Borodulin, K; Harald, K; Jousilahti, P; Laatikainen, T; Männistö, S; Vartiainen, E

    2016-01-01

    The aim of this study was to examine population trends from 1982 to 2012 in Finland for leisure time physical activity (LTPA), commuting physical activity (CPA), occupational physical activity (OPA), and total physical activity. Furthermore, time trends in physical activity by educational levels and body mass index (BMI) categories were explored. Data were collected in independent cross-sectional population surveys, implemented every 5 years from 1982 to 2012. The data comprised 21,903 men and 24,311 women. Participants underwent a health examination and filled in questionnaires. Information on LTPA, CPA, and OPA was used both separately and combined to create an index of total physical activity. Between 1982 and 2012, high LTPA has increased in men (from 21% to 33%) and women (from 12% to 27%). High CPA and high OPA have decreased in men (from 17% to 12% and from 48% to 36%, respectively) and women (from 30% to 20% and from 26% to 21%, respectively). Total physical activity has remained fairly stable. Differences by education and BMI have increased, particularly for LTPA. Marked changes in physical activity have taken place over time. Differences in LTPA and OPA have grown wider across educational groups and BMI categories. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. High-energy infrared femtosecond pulses generated by dual-chirped optical parametric amplification.

    PubMed

    Fu, Yuxi; Takahashi, Eiji J; Midorikawa, Katsumi

    2015-11-01

    We demonstrate high-energy infrared femtosecond pulse generation by a dual-chirped optical parametric amplification (DC-OPA) scheme [Opt. Express19, 7190 (2011)]. By employing a 100 mJ pump laser, a signal pulse energy exceeding 20 mJ at a wavelength of 1.4 μm was achieved before dispersion compensation. A total output energy of 33 mJ was recorded. Under a further energy scaling condition, the signal pulse was compressed to an almost transform-limited duration of 27 fs using a fused silica prism compressor. Since the DC-OPA scheme is efficient and energy scalable, design parameters for obtaining 100 mJ level infrared pulses are presented, which are suitable as driver lasers for the energy scaling of high-order harmonic generation with sub-keV photon energy.

  19. Optical phased array configuration for an extremely large telescope.

    PubMed

    Meinel, Aden Baker; Meinel, Marjorie Pettit

    2004-01-20

    Extremely large telescopes are currently under consideration by several groups in several countries. Extrapolation of current technology up to 30 m indicates a cost of over dollars 1 billion. Innovative concepts are being explored to find significant cost reductions. We explore the concept of an Optical Phased Array (OPA) telescope. Each element of the OPA is a separate Cassegrain telescope. Collimated beams from the array are sent via an associated set of delay lines to a central beam combiner. This array of small telescope elements offers the possibility of starting with a low-cost array of a few rings of elements, adding structure and additional Cass elements until the desired diameter telescope is attained. We address the salient features of such an extremely large telescope and cost elements relative to more conventional options.

  20. Does Aerobic Exercise Increase 24-Hour Ambulatory Blood Pressure Among Workers With High Occupational Physical Activity?-A RCT.

    PubMed

    Korshøj, Mette; Krause, Niklas; Clays, Els; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas

    2017-04-01

    High occupational physical activity (OPA) increases cardiovascular risk and aerobic exercise has been recommended for reducing this risk. This paper investigates the effects of an aerobic exercise intervention on 24-hour ambulatory blood pressure (ABP) among cleaners with high OPA. Hundred and sixteen cleaners between 18 and 65 years were randomized. During the 4-month intervention period, the aerobic exercise group (AE) (n = 57) performed worksite aerobic exercise (2 × 30 minutes/week), while the reference group (REF) (n = 59) attended lectures. Between-group differences in 4-month ABP changes were evaluated by intention-to-treat analysis using a repeated-measure 2 × 2 multiadjusted mixed-models design. Relative to REF, 24-hour ABP significantly increased in AE: systolic 3.6 mm Hg (95% confidence interval (CI) 1.6-5.7) and diastolic 2.3 mm Hg (95% CI 0.9-3.8). Cleaners with high aerobic workload exhibited particularly high 24-hour ABP increases: systolic 6.0 mm Hg (95% CI 2.4-9.6), and diastolic 3.8 mm Hg (95% CI 1.3-6.4). Aerobic exercise increased 24-hour ABP among cleaners. This adverse effect raises questions about the safety and intended benefits of aerobic exercise, especially among workers with high OPA and a demanding aerobic workload. http://www.controlled-trials.com/ISRCTN86682076. Unique identifier ISRCTN86682076. Trial Number ISRCTN86682076. © The Author 2017. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.

  1. Humanizing Outgroups Through Multiple Categorization

    PubMed Central

    Prati, Francesca; Crisp, Richard J.; Meleady, Rose; Rubini, Monica

    2016-01-01

    In three studies, we examined the impact of multiple categorization on intergroup dehumanization. Study 1 showed that perceiving members of a rival university along multiple versus simple categorical dimensions enhanced the tendency to attribute human traits to this group. Study 2 showed that multiple versus simple categorization of immigrants increased the attribution of uniquely human emotions to them. This effect was explained by the sequential mediation of increased individuation of the outgroup and reduced outgroup threat. Study 3 replicated this sequential mediation model and introduced a novel way of measuring humanization in which participants generated attributes corresponding to the outgroup in a free response format. Participants generated more uniquely human traits in the multiple versus simple categorization conditions. We discuss the theoretical implications of these findings and consider their role in informing and improving efforts to ameliorate contemporary forms of intergroup discrimination. PMID:26984016

  2. 30 CFR 253.1 - What is the purpose of this part?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What is the purpose of this part? 253.1 Section 253.1 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL... the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

  3. 30 CFR 553.1 - What is the purpose of this part?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 553.1 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 553.1 What is the purpose of this part...) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

  4. 30 CFR 553.1 - What is the purpose of this part?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 553.1 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 553.1 What is the purpose of this part...) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

  5. 30 CFR 553.1 - What is the purpose of this part?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 553.1 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 553.1 What is the purpose of this part...) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

  6. 2017 Workplace and Gender Relations Survey of Reserve Component Members: Tabulations of Responses

    DTIC Science & Technology

    2018-04-30

    2017 Workplace and Gender Relations Survey of Reserve Component Members Tabulations of Responses Additional copies of this report may be...http://www.dtic.mil/dtic/order.html Ask for report by DTIC# OPA Report No. 2018-012 April 2018 2017 Workplace and Gender Relations Survey of...Alexandria, VA 22350-4000 2017 Workplace and Gender Relations Survey of Reserve Component Members ii OPA Acknowledgments The Office of People Analytics

  7. Entanglement-seeded, dual, optical parametric amplification: Applications to quantum imaging and metrology

    NASA Astrophysics Data System (ADS)

    Glasser, Ryan T.; Cable, Hugo; Dowling, Jonathan P.; de Martini, Francesco; Sciarrino, Fabio; Vitelli, Chiara

    2008-07-01

    The study of optical parametric amplifiers (OPAs) has been successful in describing and creating nonclassical light for use in fields such as quantum metrology and quantum lithography [Agarwal , J. Opt. Soc. Am. B 24, 2 (2007)]. In this paper we present the theory of an OPA scheme utilizing an entangled state input. The scheme involves two identical OPAs seeded with the maximally path-entangled ∣N00N⟩ state (∣2,0⟩+∣0,2⟩)/2 . The stimulated amplification results in output state probability amplitudes that have a dependence on the number of photons in each mode, which differs greatly from two-mode squeezed vacuum. A large family of entangled output states are found. Specific output states allow for the heralded creation of N=4 N00N states, which may be used for quantum lithography, to write sub-Rayleigh fringe patterns, and for quantum interferometry, to achieve Heisenberg-limited phase measurement sensitivity.

  8. Thermal effects in high average power optical parametric amplifiers.

    PubMed

    Rothhardt, Jan; Demmler, Stefan; Hädrich, Steffen; Peschel, Thomas; Limpert, Jens; Tünnermann, Andreas

    2013-03-01

    Optical parametric amplifiers (OPAs) have the reputation of being average power scalable due to the instantaneous nature of the parametric process (zero quantum defect). This Letter reveals serious challenges originating from thermal load in the nonlinear crystal caused by absorption. We investigate these thermal effects in high average power OPAs based on beta barium borate. Absorption of both pump and idler waves is identified to contribute significantly to heating of the nonlinear crystal. A temperature increase of up to 148 K with respect to the environment is observed and mechanical tensile stress up to 40 MPa is found, indicating a high risk of crystal fracture under such conditions. By restricting the idler to a wavelength range far from absorption bands and removing the crystal coating we reduce the peak temperature and the resulting temperature gradient significantly. Guidelines for further power scaling of OPAs and other nonlinear devices are given.

  9. On the frictional (in) stability of clay-bearing faults

    NASA Astrophysics Data System (ADS)

    Violay, M.; Orellana, F.; Scuderi, M. M.; Collettini, C.

    2016-12-01

    Opalinus clay (OPA) is shale rock studied under the context of deep geological disposal by The Mont Terri Laboratory research program in Switzerland. Despite its favorable hydro-mechanical properties, the presence of a large tectonic fault system intersecting the rock formation arises questions over the long-term safety performance of a nuclear waste repository, in terms of possible leakages and the possibility of earthquakes triggered by fault instability. To study the frictional stability of OPA, we have performed velocity steps (1-300 μm/s) and slide-hold-slide tests (1-10000 s) on simulated gouge and intact samples - sheared parallel and perpendicular to foliation - at different normal stresses (4 - 30 MPa). To understand the deformation mechanisms, we have analyzed the microstructures of the sheared samples trough optical and SE microscopy. Results reported peak and steady state friction values ranging from 0.21 to 0.52 and from 0.14 to 0.39 respectively. Consistently, samples with well-developed layering showed lower friction values than gouge samples even though they have the same mineralogical composition. At all normal stresses, velocity dependence tests on gouge showed a velocity strengthening regime, whereas, intact samples developed both velocity-strengthening and velocity-weakening regimes. Finally, we have recorded near zero healing values for both intact and powdered samples at different normal stress. However, a complex evolution from negative to positive frictional healing rate, with an inflexion holding time of 300 s, has been observed. In conclusion, our data suggests that both the velocity strengthening regime and the near zero healing for the simulated gouge, are consistent with aseismic creep. We have also reported the possibility of unstable sliding outside the fault core accompanied by low capacity of contact regeneration, and low capacity to sustain future stress drops compared to evidence showed by experiments on simulated gouge. Moreover, microstructure analysis revealed different deformation patterns due to anisotropy of the material. Thus, the complex frictional behavior of OPA highlights the need for further experiments in order to better evaluate the seismic risk during long-term nuclear waste disposal within the OPA clay formation.

  10. UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-β1-FAP-α.

    PubMed

    Wäster, Petra; Orfanidis, Kyriakos; Eriksson, Ida; Rosdahl, Inger; Seifert, Oliver; Öllinger, Karin

    2017-08-08

    Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed. Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-β1. Fibroblast activation protein-α expression was induced by UVR in melanocytes of human skin. The FAP-α expression was regulated by UVR-induced release of TGF-β1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-α mediated ECM degradation and facilitated tumour cell dissemination. Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-β1 and FAP-α expression, promoting cancer cell dissemination and melanoma metastatic spread.

  11. A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes.

    PubMed

    Li, Qiuhong; Hutchins, Andrew P; Chen, Yong; Li, Shengbiao; Shan, Yongli; Liao, Baojian; Zheng, Dejin; Shi, Xi; Li, Yinxiong; Chan, Wai-Yee; Pan, Guangjin; Wei, Shicheng; Shu, Xiaodong; Pei, Duanqing

    2017-05-03

    Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks the EMT as well as DE formation. We then identify SNAI1 as the key EMT transcriptional factor required for the specification of DE. Genetic ablation of SNAI1 in hESCs does not affect the maintenance of pluripotency or neural differentiation, but completely disrupts the formation of DE. These results reveal a critical mesenchymal phase during the acquisition of DE, highlighting a role for sequential EMT-METs in both differentiation and reprogramming.

  12. Ground and Airborne Methane Measurements with an Optical Parametric Amplifier

    NASA Technical Reports Server (NTRS)

    Numata, Kenji

    2012-01-01

    We report on ground and airborne atmospheric methane measurements with a differential absorption lidar using an optical parametric amplifier (OPA). Methane is a strong greenhouse gas on Earth and its accurate global mapping is urgently needed to understand climate change. We are developing a nanosecond-pulsed OPA for remote measurements of methane from an Earth-orbiting satellite. We have successfully demonstrated the detection of methane on the ground and from an airplane at approximately 11-km altitude.

  13. Competing collinear and noncollinear interactions in chirped quasi-phase-matched optical parametric amplifiers

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

    Charbonneau-Lefort, Mathieu; Afeyan, Bedros; Fejer, M. M.

    Chirped quasi-phase-matched optical parametric amplifiers (chirped QPM OPAs) are investigated experimentally. The measured collinear gain is constant over a broad bandwidth, which makes these devices attractive candidates for use in femtosecond amplifier systems. The experiment also shows that chirped QPM OPAs support noncollinear gain-guided modes. These modes can dominate the desired collinear gain and generate intense parametric fluorescence. Finally, design guidelines to mitigate these parasitic processes are discussed.

  14. Transporting US oil imports: The impact of oil spill legislation on the tanker market. Draft final report

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

    Rowland, P.J.

    1992-05-01

    The Oil Pollution Act of 1990 (``OPA``) and an even more problematic array of State pollution laws have raised the cost, and risk, of carrying oil into and out of the US. This report, prepared under contract to the US Department of energy`s Office of Domestic and International Policy, examines the impact of Federal and State oil spill legislation on the tanker market. It reviews the role of marine transportation in US oil supply, explores the OPA and State oil spill laws, studies reactions to OPA in the tanker and tank barge industries and in related industries such as insurancemore » and ship finance, and finally, discusses the likely developments in the years ahead. US waterborne oil imports amounted to 6.5 million B/D in 1991, three-quarters of which was crude oil. Imports will rise by almost 3 million B/D by 2000 according to US Department of energy forecasts, with most of the crude oil growth after 1995. Tanker demand will grow even faster: most of the US imports and the increased traffic to other world consuming regions will be on long-haul trades. Both the number of US port calls by tankers and the volume of offshore lightering will grow. Every aspect of the tanker industry`s behavior is affected by OPA and a variety of State pollution laws.« less

  15. Transporting US oil imports: The impact of oil spill legislation on the tanker market

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

    Rowland, P.J.

    1992-05-01

    The Oil Pollution Act of 1990 ( OPA'') and an even more problematic array of State pollution laws have raised the cost, and risk, of carrying oil into and out of the US. This report, prepared under contract to the US Department of energy's Office of Domestic and International Policy, examines the impact of Federal and State oil spill legislation on the tanker market. It reviews the role of marine transportation in US oil supply, explores the OPA and State oil spill laws, studies reactions to OPA in the tanker and tank barge industries and in related industries such asmore » insurance and ship finance, and finally, discusses the likely developments in the years ahead. US waterborne oil imports amounted to 6.5 million B/D in 1991, three-quarters of which was crude oil. Imports will rise by almost 3 million B/D by 2000 according to US Department of energy forecasts, with most of the crude oil growth after 1995. Tanker demand will grow even faster: most of the US imports and the increased traffic to other world consuming regions will be on long-haul trades. Both the number of US port calls by tankers and the volume of offshore lightering will grow. Every aspect of the tanker industry's behavior is affected by OPA and a variety of State pollution laws.« less

  16. Possible mechanisms for the relative efficacies of ortho-phthalaldehyde and glutaraldehyde against glutaraldehyde-resistant Mycobacterium chelonae.

    PubMed

    Walsh, S E; Maillard, J Y; Russell, A D; Hann, A C

    2001-07-01

    This investigation compared glutaraldehyde (GTA)-sensitive and -resistant strains of Mycobacterium chelonae and examined the effects of pretreatment of GTA-sensitive and -resistant strains of Myco. chelonae with chemical agents that interfere with cell wall synthesis. When exposed to 2% (v/v) GTA at 25 degrees C, GTA-resistant strains of Myco. chelonae dried on to glass carriers were not inactivated to any significant extent. By contrast, GTA-sensitive strains of Myco. chelonae and a strain of Myco. terrae suffered a > 6 log reduction in viability in 5 min. However, ortho-phthalaldehyde (OPA; 0.5% w/v) achieved a corresponding inactivation against two GTA-resistant strains within 5-10 and 10-20 min, respectively. Electron microscopy, using a non-aldehyde fixation process and also negative staining, failed to detect any extensive changes in GTA-sensitive and -resistant cultures exposed to GTA or OPA. Thin-layer chromatography was unsuccessful in detecting differences between GTA-resistant and -sensitive strains of Myco. chelonae. However, pretreatment of GTA-resistant cells with mycobacterial cell wall synthesis inhibitors increased their subsequent susceptibility further to OPA but not to GTA. Ortho-phthalaldehyde is an effective new biocidal agent that, at its in-use concentration, is rapidly bactericidal to non-sporulating bacteria, including GTA-sensitive and -resistant mycobacteria. Pretreatment of GTA-resistant cells with mycobacterial cell wall synthesis inhibitors increased their subsequent susceptibility to OPA but not to GTA.

  17. Femtosecond optical parametric amplification in BBO and KTA driven by a Ti:sapphire laser for LIDT testing and diagnostic development

    NASA Astrophysics Data System (ADS)

    Meadows, Alexander R.; Cupal, Josef; Hříbek, Petr; Durák, Michal; Kramer, Daniel; Rus, Bedřich

    2017-05-01

    We present the design of a collinear femtosecond optical parametric amplification (OPA) system producing a tunable output at wavelengths between 1030 nm and 1080 nm from a Ti:Sapphire pump laser at a wavelength of 795 nm. Generation of a supercontinuum seed pulse is followed by one stage of amplification in Beta Barium Borate (BBO) and two stages of amplification in Potassium Titanyle Arsenate (KTA), resulting in a 225 μJ output pulse with a duration of 90 fs. The output of the system has been measured by self-referenced spectral interferometry to yield the complete spectrum and spectral phase of the pulse. When compared to KTP, the greater transparency of KTA in the spectral range from 3 - 4 μm allows for reduced idler absorption and enhanced gain from the OPA process when it is pumped by the fundamental frequency of a Ti:sapphire laser. In turn, the use of the Ti:sapphire fundamental at 795 nm as a pump improves the efficiency with which light can be converted to wavelengths between 1030 nm and 1080 nm and subsequently used to test components for Nd-based laser systems. This OPA system is operated at 1 kHz for diagnostic development and laser-induced damage threshold testing of optical components for the ELI-Beamlines project.

  18. Exploring Chemistry in Microcompartments Using Guided Droplet Collisions in a Branched Quadrupole Trap Coupled to a Single Droplet, Paper Spray Mass Spectrometer

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

    Jacobs, Michael I.; Davies, James F.; Lee, Lance

    Recent studies suggest that reactions in aqueous microcompartments can occur at significantly different rates than those in the bulk. Most studies have used electrospray to generate a polydisperse source of highly charged microdroplets, leading to multiple confounding factors potentially influencing reaction rates (e.g., evaporation, charge, and size). Thus, the underlying mechanism for the observed enhancement remains unclear. We present a new type of electrodynamic balance - the branched quadrupole trap (BQT) - which can be used to study reactions in microdroplets in a controlled environment. The BQT allows for condensed phase chemical reactions to be initiated by colliding droplets withmore » different reactants and levitating the merged droplet indefinitely. The performance of the BQT is characterized in several ways. Sub-millisecond mixing times as fast as ~400 μs are measured for low velocity (~0.1 m/s) collisions of droplets with <40 μm diameters. The reaction of o-phthalaldehyde (OPA) with alanine in the presence of dithiolthreitol is measured using both fluorescence spectroscopy and single droplet paper spray mass spectrometry. The bimolecular rate constant for reaction of alanine with OPA is found to be 84 ± 10 and 67 ± 6 M -1s -1 in a 30 μm radius droplet and bulk solution, respectively, which demonstrates that bimolecular reaction rate coefficients can be quantified using merged microdroplets and that merged droplets can be used to study rate enhancements due to compartmentalization. Products of the reaction of OPA with alanine are detected in single droplets using paper spray mass spectrometry. Finally, we demonstrate that single droplets with <100 pg of analyte can easily be studied using single droplet mass spectrometry.« less

  19. Exploring Chemistry in Microcompartments Using Guided Droplet Collisions in a Branched Quadrupole Trap Coupled to a Single Droplet, Paper Spray Mass Spectrometer

    DOE PAGES

    Jacobs, Michael I.; Davies, James F.; Lee, Lance; ...

    2017-10-19

    Recent studies suggest that reactions in aqueous microcompartments can occur at significantly different rates than those in the bulk. Most studies have used electrospray to generate a polydisperse source of highly charged microdroplets, leading to multiple confounding factors potentially influencing reaction rates (e.g., evaporation, charge, and size). Thus, the underlying mechanism for the observed enhancement remains unclear. We present a new type of electrodynamic balance - the branched quadrupole trap (BQT) - which can be used to study reactions in microdroplets in a controlled environment. The BQT allows for condensed phase chemical reactions to be initiated by colliding droplets withmore » different reactants and levitating the merged droplet indefinitely. The performance of the BQT is characterized in several ways. Sub-millisecond mixing times as fast as ~400 μs are measured for low velocity (~0.1 m/s) collisions of droplets with <40 μm diameters. The reaction of o-phthalaldehyde (OPA) with alanine in the presence of dithiolthreitol is measured using both fluorescence spectroscopy and single droplet paper spray mass spectrometry. The bimolecular rate constant for reaction of alanine with OPA is found to be 84 ± 10 and 67 ± 6 M -1s -1 in a 30 μm radius droplet and bulk solution, respectively, which demonstrates that bimolecular reaction rate coefficients can be quantified using merged microdroplets and that merged droplets can be used to study rate enhancements due to compartmentalization. Products of the reaction of OPA with alanine are detected in single droplets using paper spray mass spectrometry. Finally, we demonstrate that single droplets with <100 pg of analyte can easily be studied using single droplet mass spectrometry.« less

  20. Copper deficiency alters cell bioenergetics and induces mitochondrial fusion through up-regulation of MFN2 and OPA1 in erythropoietic cells

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

    Bustos, Rodrigo I.; Jensen, Erik L.; Ruiz, Lina M.

    2013-08-02

    Highlights: •In copper deficiency, cell proliferation is not affected. In turn, cell differentiation is impaired. •Enlarged mitochondria are due to up-regulation of MNF2 and OPA1. •Mitochondria turn off respiratory chain and ROS production. •Energy metabolism switch from mitochondria to glycolysis. -- Abstract: Copper is essential in cell physiology, participating in numerous enzyme reactions. In mitochondria, copper is a cofactor for respiratory complex IV, the cytochrome c oxidase. Low copper content is associated with anemia and the appearance of enlarged mitochondria in erythropoietic cells. These findings suggest a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis, which has notmore » been explored so far. Here, we describe that bathocuproine disulfonate-induced copper deficiency does not alter erythropoietic cell proliferation nor induce apoptosis. However it does impair erythroid differentiation, which is associated with a metabolic switch between the two main energy-generating pathways. That is, from mitochondrial function to glycolysis. Switching off mitochondria implies a reduction in oxygen consumption and ROS generation along with an increase in mitochondrial membrane potential. Mitochondrial fusion proteins MFN2 and OPA1 were up-regulated along with the ability of mitochondria to fuse. Morphometric analysis of mitochondria did not show changes in total mitochondrial biomass but rather bigger mitochondria because of increased fusion. Similar results were also obtained with human CD34+, which were induced to differentiate into red blood cells. In all, we have shown that adequate copper levels are important for maintaining proper mitochondrial function and for erythroid differentiation where the energy metabolic switch plus the up-regulation of fusion proteins define an adaptive response to copper deprivation to keep cells alive.« less

  1. Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives.

    PubMed

    Farris, Samantha G; Zvolensky, Michael J; Beckham, Jean C; Vujanovic, Anka A; Schmidt, Norman B

    2014-01-01

    Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association.

  2. Trauma Exposure and Cigarette Smoking: The Impact of Negative Affect and Affect-Regulatory Smoking Motives

    PubMed Central

    Farris, Samantha G.; Zvolensky, Michael J.; Beckham, Jean C.; Vujanovic, Anka A.; Schmidt, Norman B.

    2014-01-01

    Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association. PMID:25299617

  3. Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling

    PubMed Central

    Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

    2013-01-01

    Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways. PMID:23764850

  4. Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling.

    PubMed

    Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

    2013-06-13

    Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways.

  5. Ultrafast polarisation spectroscopy of photoinduced charges in a conjugated polymer

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

    Bakulin, A A; Loosdrecht, P van; Pshenichnikov, M S

    2009-07-31

    Tunable optical parametric generators and amplifiers (OPA), proposed and developed by Akhmanov and his colleagues, have become the working horses in exploration of dynamical processes in physics, chemistry, and biology. In this paper, we demonstrate the possibility of using ultrafast polarisation-sensitive two-colour spectroscopy, performed with a set of two OPAs, to study charge photogeneration and transport in conjugated polymers and their donor-acceptor blends. (special issue devoted to the 80th birthday of S.A. Akhmanov)

  6. Abscisic acid promotes proteasome-mediated degradation of the transcription coactivator NPR1 in Arabidopsis thaliana.

    PubMed

    Ding, Yezhang; Dommel, Matthew; Mou, Zhonglin

    2016-04-01

    Proteasome-mediated turnover of the transcription coactivator NPR1 is pivotal for efficient activation of the broad-spectrum plant immune responses known as localized acquired resistance (LAR) and systemic acquired resistance (SAR) in adjacent and systemic tissues, respectively, and requires the CUL3-based E3 ligase and its adaptor proteins, NPR3 and NPR4, which are receptors for the signaling molecule salicylic acid (SA). It has been shown that SA prevents NPR1 turnover under non-inducing and LAR/SAR-inducing conditions, but how cellular NPR1 homeostasis is maintained remains unclear. Here, we show that the phytohormone abscisic acid (ABA) and SA antagonistically influence cellular NPR1 protein levels. ABA promotes NPR1 degradation via the CUL3(NPR) (3/) (NPR) (4) complex-mediated proteasome pathway, whereas SA may protect NPR1 from ABA-promoted degradation through phosphorylation. Furthermore, we demonstrate that the timing and strength of SA and ABA signaling are critical in modulating NPR1 accumulation and target gene expression. Perturbing ABA or SA signaling in adjacent tissues alters the temporal dynamic pattern of NPR1 accumulation and target gene transcription. Finally, we show that sequential SA and ABA treatment leads to dynamic changes in NPR1 protein levels and target gene expression. Our results revealed a tight correlation between sequential SA and ABA signaling and dynamic changes in NPR1 protein levels and NPR1-dependent transcription in plant immune responses. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  7. Relative judgment theory and the mediation of facial recognition: Implications for theories of eyewitness identification.

    PubMed

    McAdoo, Ryan M; Gronlund, Scott D

    2016-01-01

    Many in the eyewitness identification community believe that sequential lineups are superior to simultaneous lineups because simultaneous lineups encourage inappropriate choosing due to promoting comparisons among choices (a relative judgment strategy), but sequential lineups reduce this propensity by inducing comparisons of lineup members directly to memory rather than to each other (an absolute judgment strategy). Different versions of the relative judgment theory have implicated both discrete-state and continuous mediation of eyewitness decisions. The theory has never been formally specified, but (Yonelinas, J Exp Psychol Learn Mem Cogn 20:1341-1354, 1994) dual-process models provide one possible specification, thereby allowing us to evaluate how eyewitness decisions are mediated. We utilized a ranking task (Kellen and Klauer, J Exp Psychol Learn Mem Cogn 40:1795-1804, 2014) and found evidence for continuous mediation when facial stimuli match from study to test (Experiment 1) and when they mismatch (Experiment 2). This evidence, which is contrary to a version of relative judgment theory that has gained a lot of traction in the legal community, compels reassessment of the role that guessing plays in eyewitness identification. Future research should continue to test formal explanations in order to advance theory, expedite the development of new procedures that can enhance the reliability of eyewitness evidence, and to facilitate the exploration of task factors and emergent strategies that might influence when recognition is continuously or discretely mediated.

  8. A fast and simple spectrofluorometric method for the determination of alendronate sodium in pharmaceuticals

    PubMed Central

    Ezzati Nazhad Dolatabadi, Jafar; Hamishehkar, Hamed; de la Guardia, Miguel; Valizadeh, Hadi

    2014-01-01

    Introduction: Alendronate sodium enhances bone formation and increases osteoblast proliferation and maturation and leads to the inhibition of osteoblast apoptosis. Therefore, a rapid and simple spectrofluorometric method has been developed and validated for the quantitative determination of it. Methods: The procedure is based on the reaction of primary amino group of alendronate with o-phthalaldehyde (OPA) in sodium hydroxide solution. Results: The calibration graph was linear over the concentration range of 0.0-2.4 μM and limit of detection and limit of quantification of the method was 8.89 and 29 nanomolar, respectively. The enthalpy and entropy of the reaction between alendronate sodium and OPA showed that the reaction is endothermic and entropy favored (ΔH = 154.08 kJ/mol; ΔS = 567.36 J/mol K) which indicates that OPA interaction with alendronate is increased at elevated temperature. Conclusion: This simple method can be used as a practical technique for the analysis of alendronate in various samples. PMID:24790897

  9. Bactericidal activity of glutaraldehyde-like compounds from olive products.

    PubMed

    Medina, Eduardo; Brenes, Manuel; García, Aranzazu; Romero, Concepción; de Castro, Antonio

    2009-12-01

    The bactericidal effects of several olive compounds (nonenal, oleuropein, tyrosol, the dialdehydic form of decarboxymethyl elenolic acid either free [EDA] or linked to tyrosol [TyEDA] or to hydroxytyrosol [HyEDA]), other food phenolic compounds (catechin, epicatechin, eugenol, thymol, carvacrol, and carnosic acid), and commercial disinfectants (glutaraldehyde [GTA] and ortho-phthalaldehyde [OPA]), were tested against strains of Pseudomonas fluorescens, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. It was found that the bactericidal activities of olive GTA-like compounds (EDA, HyEDA, and TyEDA) were greater than those exerted by several food phenolic substances. Surprisingly, these olive antimicrobials were as active as the synthetic biocides GTA and OPA against the four bacteria studied. Thus, it has been proposed that the bactericidal activity of the main olive antimicrobials is primarily due to their dialdehydic structure, which is similar to that of the commercial biocides GTA and OPA. Our results clearly reveal that olive GTA-like compounds possess a strong bactericidal activity even greater than that of other food phenolic compounds or synthetic biocides.

  10. Effect of Tdap when administered before, with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial.

    PubMed

    Tashani, M; Alfelali, M; Barasheed, O; Alqahtani, A S; Heron, L; Wong, M; Rashid, H; Booy, R

    2016-11-21

    Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3-4weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3-4weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18-64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse events were reported. In conclusion, Tdap vaccination 3-4weeks before concomitant administration of PCV13 and MCV4 significantly reduced the antibody response to six of the 13 pneumococcal serotypes in adults. The trial is registered at the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000536763. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Activity coefficients from molecular simulations using the OPAS method

    NASA Astrophysics Data System (ADS)

    Kohns, Maximilian; Horsch, Martin; Hasse, Hans

    2017-10-01

    A method for determining activity coefficients by molecular dynamics simulations is presented. It is an extension of the OPAS (osmotic pressure for the activity of the solvent) method in previous work for studying the solvent activity in electrolyte solutions. That method is extended here to study activities of all components in mixtures of molecular species. As an example, activity coefficients in liquid mixtures of water and methanol are calculated for 298.15 K and 323.15 K at 1 bar using molecular models from the literature. These dense and strongly interacting mixtures pose a significant challenge to existing methods for determining activity coefficients by molecular simulation. It is shown that the new method yields accurate results for the activity coefficients which are in agreement with results obtained with a thermodynamic integration technique. As the partial molar volumes are needed in the proposed method, the molar excess volume of the system water + methanol is also investigated.

  12. High peak-power laser system tuneable from 8 to 10 μm

    NASA Astrophysics Data System (ADS)

    Gutty, François; Grisard, Arnaud; Larat, Christian; Papillon, Dominique; Schwarz, Muriel; Gérard, Bruno; Ostendorf, Ralf; Wagner, Joachim; Lallier, Eric

    2017-04-01

    A high peak-power rapidly tuneable laser system in the long-wave infrared is obtained using an external cavity quantum-cascade laser (EC-QCL) broadly tuneable from 8 to 10 μm and an optical parametric amplifier (OPA) based on quasi phase-matching in orientation-patterned gallium arsenide (OP-GaAs). To provide an efficient amplification, the nonlinear crystal is pumped by a pulsed fiber laser source. With a pump laser source tuneable around 2 μm, quasi phase-matching remains satisfied with a fixed grating period in the OP-GaAs crystal when the EC-QCL wavelength is swept from 8 to 10 μm. The OPA demonstrates parametric amplification from 8 to 10 μm and achieves output peak powers up to 140 W, with spectral linewidths below 3.5 cm-1 and a beam profile quality (M2) below 3.4 in both horizontal and vertical directions.

  13. Fiber optical parametric amplifiers in optical communication systems

    PubMed Central

    Marhic (†), Michel E; Andrekson, Peter A; Petropoulos, Periklis; Radic, Stojan; Peucheret, Christophe; Jazayerifar, Mahmoud

    2015-01-01

    The prospects for using fiber optical parametric amplifiers (OPAs) in optical communication systems are reviewed. Phase-insensitive amplifiers (PIAs) and phase-sensitive amplifiers (PSAs) are considered. Low-penalty amplification at/or near 1 Tb/s has been achieved, for both wavelength- and time-division multiplexed formats. High-quality mid-span spectral inversion has been demonstrated at 0.64 Tb/s, avoiding electronic dispersion compensation. All-optical amplitude regeneration of amplitude-modulated signals has been performed, while PSAs have been used to demonstrate phase regeneration of phase-modulated signals. A PSA with 1.1-dB noise figure has been demonstrated, and preliminary wavelength-division multiplexing experiments have been performed with PSAs. 512 Gb/s have been transmitted over 6,000 km by periodic phase conjugation. Simulations indicate that PIAs could reach data rate x reach products in excess of 14,000 Tb/s × km in realistic wavelength-division multiplexed long-haul networks. Technical challenges remaining to be addressed in order for fiber OPAs to become useful for long-haul communication networks are discussed. PMID:25866588

  14. FIRST NEW SOLAR MODELS WITH OPAS OPACITY TABLES

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

    Le Pennec, M.; Turck-Chièze, S.; Salmon, S.

    Stellar seismology appears more and more as a powerful tool for a better determination of the fundamental properties of solar-type stars. However, the particular case of the Sun is still challenging. For about a decade now, the helioseismic sound-speed determination has continued to disagree with the standard solar model (SSM) prediction, questioning the reliability of this model. One of the sources of uncertainty could be in the treatment of the transport of radiation from the solar core to the surface. In this Letter, we use the new OPAS opacity tables, recently available for solar modeling, to address this issue. Wemore » discuss first the peculiarities of these tables, then we quantify their impact on the solar sound-speed and density profiles using the reduced OPAS tables taken on the grids of the OPAL ones. We use the two evolution codes, Modules for Experiments in Stellar Astrophysics and Code Liégeois d’Evolution Stellaire, that led to similar conclusions in the solar radiative zone. In comparison to commonly used OPAL opacity tables, the new solar models are computed for the most recent photospheric composition with OPAS tables and present improvements to the location of the base of the convective zone and to the description of the solar radiative zone in comparison to the helioseismic observations, even if the differences in the Rosseland mean opacity do not exceed 6%. We finally carry out a comparison to a solar model computed with the OP opacity tables.« less

  15. Regioselective Cu(I)-catalyzed tandem A3-coupling/decarboxylative coupling to 3-amino-1,4-enynes.

    PubMed

    Feng, Huangdi; Ermolat'ev, Denis S; Song, Gonghua; Van der Eycken, Erik V

    2012-04-06

    An efficient and novel copper-mediated protocol for the synthesis of 3-amino-1,4-enynes from glyoxylic acid, an amine, and an alkyne was developed. This new reaction involving two sequential C-C bond formations is air and moisture tolerant and proceeds via a tandem A(3)-coupling and a selective decarboxylative coupling.

  16. Educating the Educator: Teaching Airway Adjunct Techniques in Athletic Training

    ERIC Educational Resources Information Center

    Berry, David C.; Seitz, S. Robert

    2011-01-01

    The 5th edition of the "Athletic Training Education Competencies" ("Competencies") now requires athletic training educators (ATEs) to introduce into the curriculum various types of airway adjuncts including: (1) oropharyngeal airways (OPA), (2) nasopharyngeal airways (NPA), (3) supraglottic airways (SGA), and (4) suction. The addition of these…

  17. 33 CFR 1.01-80 - FWPCA and OPA 90 delegations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... vessels; with or without warrant, arrest any person who, in the Commander's presence or view, violates a... any person who, in the Commander's presence or view, violates a provision of section 311 of the FWPCA... On-Scene Coordinator by the applicable Regional Contingency Plan is delegated authority pursuant to...

  18. 28 CFR 16.79 - Exemption of Pardon Attorney System.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... System (JUSTICE/OPA-001) is to enable the Justice Department to prepare reports and recommendations to... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exemption of Pardon Attorney System. 16... OR INFORMATION Exemption of Records Systems Under the Privacy Act § 16.79 Exemption of Pardon...

  19. Towards Terawatt Sub-Cycle Long-Wave Infrared Pulses via Chirped Optical Parametric Amplification and Indirect Pulse Shaping

    PubMed Central

    Yin, Yanchun; Chew, Andrew; Ren, Xiaoming; Li, Jie; Wang, Yang; Wu, Yi; Chang, Zenghu

    2017-01-01

    We present an approach for both efficient generation and amplification of 4–12 μm pulses by tailoring the phase matching of the nonlinear crystal Zinc Germanium Phosphide (ZGP) in a narrowband-pumped optical parametric chirped pulse amplifier (OPCPA) and a broadband-pumped dual-chirped optical parametric amplifier (DC-OPA), respectively. Preliminary experimental results are obtained for generating 1.8–4.2 μm super broadband spectra, which can be used to seed both the signal of the OPCPA and the pump of the DC-OPA. The theoretical pump-to-idler conversion efficiency reaches 27% in the DC-OPA pumped by a chirped broadband Cr2+:ZnSe/ZnS laser, enabling the generation of  Terawatt-level 4–12 μm pulses with an available large-aperture ZGP. Furthermore, the 4–12 μm idler pulses can be compressed to sub-cycle pulses by compensating the tailored positive chirp of the idler pulses using the bulk compressor NaCl, and by indirectly controlling the higher-order idler phase through tuning the signal (2.4–4.0 μm) phase with a commercially available acousto-optic programmable dispersive filter (AOPDF). A similar approach is also described for generating high-energy 4–12 μm sub-cycle pulses via OPCPA pumped by a 2 μm Ho:YLF laser. PMID:28367966

  20. One- and two-photon absorption spectra of the yellow fluorescent protein citrine: effects of intramolecular electron-vibrational coupling and intermolecular interactions

    NASA Astrophysics Data System (ADS)

    Chen, Fasheng; Zhao, Xinyi; Liang, WanZhen

    2018-04-01

    Both the vibrationally resolved and statistically averaged one-photon absorption (OPA) and two-photon absorption (TPA) spectra of the anionic form of chromophore (AC) in its micro-environment of yellow fluorescent protein (YFP) Citrine have been calculated. The result comparison has been made with those of the AC model compounds in vacuo and methanol solution, which allows us to allocate the individual contribution of the intramolecular electron-vibrational coupling, the electrostatic π-stacking interaction between Tyr203 and AC, and the interaction between AC and its micro-environment to the spectra. The results reveal that the non-Condon vibronic coupling effect is responsible for the blue shift of TPA absorption maximum compared with its OPA counterpart corresponding to S0 → S1, and that the π-stacking interaction between Tyr203 and AC alters the relative intensities of TPA maxima, which further enhances the higher-energy vibronic peaks and weakens the lowest-energy peak. The statically averaged OPA and TPA spectra calculated by quantum mechanics/molecular mechanics (QM/MM) methods based on Born-Oppenheimer molecular dynamics simulation largely deviate the experimental spectral lineshapes, which further verifies the significant contribution of non-Condon vibronic coupling effect on the spectra. The interaction of individual amino acid residue or water close to AC+Tyr203 has different effects on the spectra, which may increase/decrease the excitation energy depending on its position and electronic property.

  1. Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia.

    PubMed

    Urbancikova, Ingrid; Prymula, Roman; Goldblatt, David; Roalfe, Lucy; Prymulova, Karolina; Kosina, Pavel

    2017-09-12

    Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12-15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11-12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1month post-booster. A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27). Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Optical parametric amplification of arbitrarily polarized light in periodically poled LiNbO3.

    PubMed

    Shao, Guang-hao; Song, Xiao-shi; Xu, Fei; Lu, Yan-qing

    2012-08-13

    Optical parametric amplification (OPA) of arbitrarily polarized light is proposed in a multi-section periodically poled Lithium Niobate (PPLN). External electric field is applied on selected sections to induce the polarization rotation of involved lights, thus the quasi-phase matched optical parametric processes exhibit polarization insensitivity under suitable voltage. In addition to the amplified signal wave, an idler wave with the same polarization is generated simultaneously. As an example, a ~10 times OPA showing polarization independency is simulated. Applications of this technology are also discussed.

  3. Objectively measured physical activity and 12-month trajectories of neck-shoulder pain in workers: A prospective study in DPHACTO.

    PubMed

    Hallman, David M; Birk Jørgensen, Marie; Holtermann, Andreas

    2017-05-01

    This study aimed to investigate the association between objectively measured physical activity at work and leisure and the intensity (mean level and time course) of neck-shoulder pain (NSP) over 12 months among male and female blue collar workers. Data were obtained from 625 blue collar workers from the Danish cohort DPHACTO. Physical activity was measured objectively at baseline using accelerometers. The percentage of time spent in physical activity (walking, climbing stairs, running and cycling) was calculated for both work and leisure time. Longitudinal data on the intensity of NSP (numerical rating scale 0-10) were collected using text messages every fourth week over 12 months. Linear mixed models were used to investigate the associations between occupational physical activity (OPA) and leisure time physical activity (LTPA) and the trajectories of the intensity of NSP, adjusted for individual, biomechanical and psychosocial factors, and baseline pain. OPA was not associated with the mean intensity of NSP over 12 months. LTPA was negatively associated with the mean intensity of NSP both among men ( B=-0.71, 95% CI -1.31 to -0.11) and women ( B=-0.85, 95% CI -1.57 to -0.13). Sex interactions on the 12-month trajectories of NSP showed that higher physical activity was associated with a slower reduction in NSP among men for OPA only ( B=0.03, 95% CI 0.01-0.05) and women for LTPA only ( B=0.05, 95% CI 0.00-0.09). We found that more time in LTPA was associated with a lower overall intensity of NSP over 12 months among blue collar workers. However, depending on sex and domain, high physical activity had an unfavourable effect on the course of NSP over 12 months.

  4. Acute effect on ambulatory blood pressure from aerobic exercise: a randomised cross-over study among female cleaners.

    PubMed

    Lund Rasmussen, Charlotte; Nielsen, Line; Linander Henriksen, Marie; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas; Korshøj, Mette

    2018-02-01

    High occupational physical activity (OPA) is shown to increase the risk for elevated blood pressure, cardiovascular diseases and mortality. Conversely, aerobic exercise acutely lowers the blood pressure up to 25 h post exercise. However, it is unknown if this beneficial effect also apply for workers exposed to high levels of OPA. Cleaners constitute a relevant occupational group for this investigation because of a high prevalence of OPA and cardiovascular disease. Accordingly, the objective was to investigate the acute effects on ambulatory blood pressure from a single aerobic exercise session among female cleaners. Twenty-two female cleaners were randomised to a cross-over study with a reference and an aerobic exercise session. Differences in 24-h, work hours, leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using repeated measure 2 × 2 mixed-models. After the aerobic exercise session, the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg (p < 0.01) compared to the reference session. The 24-h diastolic ABP was unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04) and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP was unaltered. A single aerobic exercise session lowered 24-h systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be beneficial for lowering the risk of hypertension among cleaners.

  5. Neisseria gonorrhoeae infects the human endocervix by activating non-muscle myosin II-mediated epithelial exfoliation

    PubMed Central

    Yu, Qian; Lin, Brian; Qiu, Jessica; Stein, Daniel C.

    2017-01-01

    Colonization and disruption of the epithelium is a major infection mechanism of mucosal pathogens. The epithelium counteracts infection by exfoliating damaged cells while maintaining the mucosal barrier function. The sexually transmitted bacterium Neisseria gonorrhoeae (GC) infects the female reproductive tract primarily from the endocervix, causing gonorrhea. However, the mechanism by which GC overcome the mucosal barrier remains elusive. Using a new human tissue model, we demonstrate that GC can penetrate into the human endocervix by inducing the exfoliation of columnar epithelial cells. We found that GC colonization causes endocervical epithelial cells to shed. The shedding results from the disassembly of the apical junctions that seal the epithelial barrier. Apical junction disruption and epithelial exfoliation increase GC penetration into the endocervical epithelium without reducing bacterial adherence to and invasion into epithelial cells. Both epithelial exfoliation and junction disruption require the activation and accumulation of non-muscle myosin II (NMII) at the apical surface and GC adherent sites. GC inoculation activates NMII by elevating the levels of the cytoplasmic Ca2+ and NMII regulatory light chain phosphorylation. Piliation of GC promotes, but the expression of a GC opacity-associated protein variant, OpaH that binds to the host surface proteins CEACAMs, inhibits GC-induced NMII activation and reorganization and Ca2+ flux. The inhibitory effects of OpaH lead to reductions in junction disruption, epithelial exfoliation, and GC penetration. Therefore, GC phase variation can modulate infection in the human endocervix by manipulating the activity of NMII and epithelial exfoliation. PMID:28406994

  6. Idler-efficiency-enhanced long-wave infrared beam generation using aperiodic orientation-patterned GaAs gratings.

    PubMed

    Gürkan Figen, Ziya; Aytür, Orhan; Arıkan, Orhan

    2016-03-20

    In this paper, we design aperiodic gratings based on orientation-patterned gallium arsenide (OP-GaAs) for converting 2.1 μm pump laser radiation into long-wave infrared (8-12 μm) in an idler-efficiency-enhanced scheme. These single OP-GaAs gratings placed in an optical parametric oscillator (OPO) or an optical parametric generator (OPG) can simultaneously phase match two optical parametric amplification (OPA) processes, OPA 1 and OPA 2. We use two design methods that allow simultaneous phase matching of two arbitrary χ(2) processes and also free adjustment of their relative strength. The first aperiodic grating design method (Method 1) relies on generating a grating structure that has domain walls located at the zeros of the summation of two cosine functions, each of which has a spatial frequency that equals one of the phase-mismatch terms of the two processes. Some of the domain walls are discarded considering the minimum domain length that is achievable in the production process. In this paper, we propose a second design method (Method 2) that relies on discretizing the crystal length with sample lengths that are much smaller than the minimum domain length and testing each sample's contribution in such a way that the sign of the nonlinearity maximizes the magnitude sum of the real and imaginary parts of the Fourier transform of the grating function at the relevant phase mismatches. Method 2 produces a similar performance as Method 1 in terms of the maximization of the height of either Fourier peak located at the relevant phase mismatch while allowing an adjustable relative height for the two peaks. To our knowledge, this is the first time that aperiodic OP-GaAs gratings have been proposed for efficient long-wave infrared beam generation based on simultaneous phase matching.

  7. Low-Level Laser Effect on Proliferation, Migration, and Antiapoptosis of Mesenchymal Stem Cells.

    PubMed

    Yin, Kan; Zhu, Rongjia; Wang, Shihua; Zhao, Robert Chunhua

    2017-05-15

    Mesenchymal stem cells (MSCs) have been proved to be an important element in cell-based therapy. Photobiomodulation used extremely low-level lasers (LLLs) to affect the behavior of cells. The effect mechanism of LLLs on MSCs from human remained to be discovered. In this study, cell viability was assessed using MTS assays and cell cycle was evaluated by fluorescence-activated cell sorting (FACS). The influence of LLLs on mitochondrial biogenesis (fission or fusion) and function (ATP, reactive oxygen species [ROS], nitric oxide [NO]) was evaluated by transmission electron microscope, FACS, quantitative real time polymerase chain reaction (q-PCR), and immunocytochemistry. Cell migration and cytoskeleton alteration (actin and tubulin) were evaluated using transwell assay, immunocytochemistry, enzyme-linked immunosorbent assay, and western blotting. Cell apoptosis was evaluated using FACS, immunocytochemistry, and western blotting. We investigated that certain influence of LLLs on MSCs in vitro 6 or 24 h after 1 h of LLL irradiation. The mechanism of the effects included proliferation rate increase mediated by increased S phase proportion; mitochondrial biogenesis and function alteration mediated by fusion (Mfn1, Mfn2, and Opa-1) and fission (Fis1, Drp-1, and MTP18)-related proteins, NRF1, TFAM, PGC-1a, and upregulated intracellular ROS and NO concentration; migration acceleration through the ERK1/2 and FAK pathway and upregulation of growth factors such as HGF and PDGF; and resistance to apoptosis with increased Bcl-2 and decreased Bax, or through tunneling nanotube formation between LLL-treated MSCs and 5-fluorouracil-induced apoptotic MSCs. These observations suggested that LLLs enhanced stem cell survival and therapeutic function, which could appear to be an innovative pretreatment in the application of MSCs.

  8. Poor Performance on Serial Visual Tasks in Persons with Reading Disabilities: Impaired Working Memory?

    ERIC Educational Resources Information Center

    Ram-Tsur, Ronit; Faust, Miriam; Zivotofsky, Ari Z.

    2008-01-01

    The present study investigates the performance of persons with reading disabilities (PRD) on a variety of sequential visual-comparison tasks that have different working-memory requirements. In addition, mediating relationships between the sequential comparison process and attention and memory skills were looked for. Our findings suggest that PRD…

  9. Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older.

    PubMed

    Jackson, Lisa A; Gurtman, Alejandra; van Cleeff, Martin; Frenck, Robert W; Treanor, John; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2013-08-02

    Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Association between Mitofusin 2 Gene Polymorphisms and Late-Onset Alzheimer's Disease in the Korean Population

    PubMed Central

    Kim, Young Jong; Park, Jin Kyung; Kang, Won Sub; Kim, Su Kang; Han, Changsu; Na, Hae Ri; Park, Hae Jeong; Kim, Jong Woo; Kim, Young Youl; Park, Moon Ho

    2017-01-01

    Objective Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. Methods One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). Results Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. Conclusion These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD. PMID:28096879

  11. In-capillary derivatization with o-phthalaldehyde in the presence of 3-mercaptopropionic acid for the simultaneous determination of monosodium glutamate, benzoic acid, and sorbic acid in food samples via capillary electrophoresis with ultraviolet detection.

    PubMed

    Aung, Hnin-Pwint; Pyell, Ute

    2016-06-03

    For the rapid simultaneous determination of monosodium glutamate (MSG), benzoic acid (BA), and sorbic acid (SA) in canned food and other processed food samples, we developed a method that combines in-capillary derivatization with separation by capillary electrophoresis. This method employs the rapid derivatization of MSG with o-phthalaldehyde (OPA) in the presence of 3-mercaptopropionic acid (3-MPA) and enables the detection of the resulting OPA-MSG derivative and of non-derivatized BA and SA at 230nm. The composition of the background electrolyte and the parameters of derivatization and separation are as follows: 25mM borax containing 5mM OPA and 6mM 3-MPA, separation voltage 25mV, injection at 30mbar for 20s, and column temperature 25°C. Because of the high reaction rate and suitably adapted effective electrophoretic mobilities, band broadening due to the derivatization reaction at the start of the separation process is kept to a minimum. The optimized method is validated with respect to LOD, LOQ, linearity, recovery, and precision. This method can be applied to real samples such as soy, fish, oyster and sweet and sour chili sauces after application of appropriate clean-up steps. Mechanisms of zone broadening and zone focusing are discussed showing the validity of the employed theoretical approach regarding the dependence of the peak shape for OPA-MSG on the concentration of MSG in the sample. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. How Does Mentoring Contribute to Gen Y Employees’ Intention to Stay? An Indian Perspective

    PubMed Central

    Naim, Mohammad Faraz; Lenka, Usha

    2017-01-01

    The present study is aimed at investigating the impact of mentoring on intention to stay of Gen Y employees working in Indian IT industry. Also, the mediating roles of perceived organization support and affective commitment are examined. Primary data were collected from a sample of 314 Gen Y employees (born between 1980-2000) from IT industry in Delhi, NCR India. Data analysis was carried out using AMOS and SPSS to test sequential mediation. Findings reveal that mentoring has a direct influence on intention to stay of Gen Y employees and perceived organization support and affective commitment sequentially mediate the relationship between the two. This study contributes to the literature on mentoring, perceived organization support, affective commitment, and intention to stay. PMID:28580029

  13. Sequential lignin depolymerization by combination of biocatalytic and formic acid/formate treatment steps.

    PubMed

    Gasser, Christoph A; Čvančarová, Monika; Ammann, Erik M; Schäffer, Andreas; Shahgaldian, Patrick; Corvini, Philippe F-X

    2017-03-01

    Lignin, a complex three-dimensional amorphous polymer, is considered to be a potential natural renewable resource for the production of low-molecular-weight aromatic compounds. In the present study, a novel sequential lignin treatment method consisting of a biocatalytic oxidation step followed by a formic acid-induced lignin depolymerization step was developed and optimized using response surface methodology. The biocatalytic step employed a laccase mediator system using the redox mediator 1-hydroxybenzotriazole. Laccases were immobilized on superparamagnetic nanoparticles using a sorption-assisted surface conjugation method allowing easy separation and reuse of the biocatalysts after treatment. Under optimized conditions, as much as 45 wt% of lignin could be solubilized either in aqueous solution after the first treatment or in ethyl acetate after the second (chemical) treatment. The solubilized products were found to be mainly low-molecular-weight aromatic monomers and oligomers. The process might be used for the production of low-molecular-weight soluble aromatic products that can be purified and/or upgraded applying further downstream processes.

  14. Two-photon absorption in conjugated energetic molecule

    DOE PAGES

    Bjorgaard, Josiah August; Sifain, Andrew; Nelson, Tammie Renee; ...

    2016-06-03

    Time-dependent density functional theory (TD-DFT) is used to investigate the relationship between molecular structure and one- and two-photon absorption (OPA and TPA, respectively) properties in novel and recently synthesized conjugated energetic molecules (CEMs). The molecular structure of CEMs can be strategically altered to influence the heat of formation and oxygen balance, two factors that can contribute to the sensitivity and strength of an explosive material. OPA and TPA are sensitive to changes in molecular structure as well, influencing optical range of excitation. We find calculated vertical excitation energies in good agreement with experiment for most molecules. Peak TPA intensities aremore » significant and on the order of 102 GM. Natural transition orbitals for essential electronic states defining TPA peaks of relatively large intensity to examine the character of relevant transitions. Minor modification of molecular substituents, such as additional oxygen and other functional groups, produces significant changes in electronic structure, OPA, TPA, and improves the oxygen balance. Results show that select molecules are apt to nonlinear absorption, opening the possibility for controlled, direct optical initiation of CEMs through photochemical pathways.« less

  15. Optical tristability in a hybrid optomechanical system

    NASA Astrophysics Data System (ADS)

    Asghari Nejad, A.; Askari, H. R.; Baghshahi, H. R.

    2018-05-01

    In this paper, we investigate a hybrid optomechanical system consisting of two cavities, which one of them is an optomechanical cavity that includes an optical parametric amplifier (OPA) and the other is a traditional cavity which contains an atomic medium. Hamiltonian of the system is written in a rotating frame with a rotation frequency of the frequency of input field to the system. Using Heisenberg-Langevin equations of motion, the dynamics of the system is described. Applying the steady-state conditions leads to a system of equations of the mean values of the operators of the system. The stability condition of the system is satisfied numerically and behavior of optomechanical cavity is investigated in different situations to find the effect of changing of the parameters of the system on the type of its stability. We show proposed system has the capability of tristable behavior, where, the gain coefficient of OPA acts as a switch in changing the bistability of the system to a tristable manner. The building block of the tristability in this system can be figured out as the enhanced nonlinearity of the system due to the presence of OPA.

  16. 78 FR 44561 - Ortho-Phthalaldehyde; Receipt of Application for Emergency Exemption, Solicitation of Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-24

    ... code 111). Animal production (NAICS code 112). Food manufacturing (NAICS code 311). Pesticide manufacturing (NAICS code 32532). B. What should I consider as I prepare my comments for EPA? 1. Submitting CBI... coolant additives. Non-use of OPA in the requested manner would leave NASA's International Space Station...

  17. 78 FR 20631 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Spill...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPA-2007-0584; FRL-9530-1] Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Spill Prevention, Control and Countermeasure..., Control and Countermeasures (SPCC) Plans (Renewal)'' (EPA ICR No. 0328.16, OMB Control No. 2050-0021) to...

  18. Trial-to-Trial Modulations of the Simon Effect in Conditions of Attentional Limitations : Evidence from Dual Tasks

    ERIC Educational Resources Information Center

    Fischer, Rico; Plessow, Franziska; Kunde, Wilfried; Kiesel, Andrea

    2010-01-01

    Interference effects are reduced after trials including response conflict. This sequential modulation has often been attributed to a top-down mediated adaptive control mechanism and/or to feature repetition mechanisms. In the present study we tested whether mechanisms responsible for such sequential modulations are subject to attentional…

  19. Ultra-wideband and high-gain parametric amplification in telecom wavelengths with an optimally mode-matched PPLN waveguide.

    PubMed

    Sua, Yong Meng; Chen, Jia-Yang; Huang, Yu-Ping

    2018-06-15

    We report a wideband optical parametric amplification (OPA) over 14 THz covering telecom S, C, and L bands with observed maximum parametric gain of 38.3 dB. The OPA is realized through cascaded second-harmonic generation and difference-frequency generation (cSHG-DFG) in a 2 cm periodically poled LiNbO 3 (PPLN) waveguide. With tailored cross section geometry, the waveguide is optimally mode matched for efficient cascaded nonlinear wave mixing. We also identify and study the effect of competing nonlinear processes in this cSHG-DFG configuration.

  20. General analysis of group velocity effects in collinear optical parametric amplifiers and generators.

    PubMed

    Arisholm, Gunnar

    2007-05-14

    Group velocity mismatch (GVM) is a major concern in the design of optical parametric amplifiers (OPAs) and generators (OPGs) for pulses shorter than a few picoseconds. By simplifying the coupled propagation equations and exploiting their scaling properties, the number of free parameters for a collinear OPA is reduced to a level where the parameter space can be studied systematically by simulations. The resulting set of figures show the combinations of material parameters and pulse lengths for which high performance can be achieved, and they can serve as a basis for a design.

  1. Intraduodenal Administration of Intact Pea Protein Effectively Reduces Food Intake in Both Lean and Obese Male Subjects

    PubMed Central

    Geraedts, Maartje C. P.; Troost, Freddy J.; Munsters, Marjet J. M.; Stegen, Jos H. C. H.; de Ridder, Rogier J.; Conchillo, Jose M.; Kruimel, Joanna W.; Masclee, Ad A. M.; Saris, Wim H. M.

    2011-01-01

    Background Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects. Methods Ten lean (BMI:23.0±0.7 kg/m2) and ten obese (BMI:33.4±1.4 kg/m2) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded. Results CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and −298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (−132.6±42 kcal; p<0.01), compared to OPA. Conclusions Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity. PMID:21931864

  2. The Effect of Social Support on Glycemic Control in Patients with Type 2 Diabetes Mellitus: The Mediating Roles of Self-Efficacy and Adherence

    PubMed Central

    Shao, Yechang; Liang, Lu; Shi, Linjing; Yu, Shouyi

    2017-01-01

    Ample evidence suggests that social support, self-efficacy, and adherence significantly, independently, and together affect glycemic control in patients with type 2 diabetes mellitus (T2DM), but the pathway from social support to glycemic control remains unclear. This study hypothesized that the effect of social support on glycemic control was mediated sequentially by self-efficacy and adherence. Patients with T2DM were recruited from two hospitals in Guangzhou, China, from January 1 to July 31, 2014, and their sociodemographic clinical data and their assessments on social support, self-efficacy, and adherence were obtained from medical records and self-completed questionnaires. Of the 532 patients who participated, 35% achieved glycemic control (i.e., HbA1c < 7%). Social support, self-efficacy, and adherence had significant correlations with each other and with glycemic control (P < 0.05). Regression analyses and structural equation modeling showed that better social support was associated to better patient self-efficacy, which, in turn, was associated with better medical adherence, which was associated with improved glycemic control, and the relationship between social support and glycemic control was sequentially and completely mediated by self-efficacy and adherence. The five goodness-of-fit indices confirmed that our data fitted the hypothesized pathway model strongly. PMID:28626769

  3. Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection

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

    Tsvitov, Marianna; Frampton, Arthur R.; Shah, Waris A.

    2007-04-10

    Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein D (gD) to cognate receptors. In this study, we characterized the observation that soluble forms of the gD ectodomain (sgD) can mediate entry of gD-deficient HSV-1. We examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to determine the order and stability of the initial interactions required for entry. Surprisingly, virus binding to GAGs did not increase the efficiency of sgD-mediated entry andmore » gD-deficient virus was capable of attaching to GAG-deficient cells in the absence of sgD. These observations suggested a novel binding interaction that may play a role in normal HSV infection.« less

  4. 2016 Workplace and Gender Relations Survey of Active Duty Members: Overview Report

    DTIC Science & Technology

    2017-05-01

    Grifka 1 Chapter 2: Survey Methodology Ms. Lisa Davis, Mr. Eric Falk, and Mr. Jeff Schneider 19 Chapter 3: Estimated Sexual Assault...assessing the gender relations environment across the Services. Study Background and Methodology Study Background The Defense Research, Surveys, and...gender discrimination. 3 Chapter 1 provides additional information on the construction of these metrics. Survey Methodology OPA conducts DoD cross

  5. Disinfection procedures: their efficacy and effect on dimensional accuracy and surface quality of an irreversible hydrocolloid impression material.

    PubMed

    Rentzia, A; Coleman, D C; O'Donnell, M J; Dowling, A H; O'Sullivan, M

    2011-02-01

    This study investigated the antibacterial efficacy and effect of 0.55% ortho-phthalaldehyde (Cidex OPA(®)) and 0.5% sodium hypochlorite (NaOCl) on the dimensional accuracy and surface quality of gypsum casts retrieved from an irreversible hydrocolloid impression material. A simulated clinical cast and technique was developed to compare the dimensional accuracy and surface quality changes of the test gypsum casts with controls. Dimensional accuracy measurements were completed between fixed points using a travelling microscope under low angle illumination at a magnification of ×3. Surface quality changes of "smooth" and "rough" areas on the cast were evaluated by means of optical profilometry. The efficacy of the disinfection procedures against Pseudomonas aeruginosa was evaluated by determining the number of colony forming units (cfu) recovered after disinfection of alginate discs inoculated with 1×10⁶cfu for defined intervals. The dimensional accuracy of the gypsum casts was not significantly affected by the disinfection protocols. Neither disinfectant solution nor immersion time had an effect on the surface roughness of the "smooth" area on the cast, however, a significant increase in surface roughness was observed with increasing immersion time for the "rough" surface. Complete elimination of viable Pseudomonas aeruginosa cells from alginate discs was obtained after 30 and 120 s immersion in Cidex OPA(®) and NaOCl, respectively. Immersion of irreversible hydrocolloid impressions in Cidex OPA(®) for 30 s was proved to be the most effective disinfection procedure. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Sequential replication-coupled destruction at G1/S ensures genome stability

    PubMed Central

    Coleman, Kate E.; Grant, Gavin D.; Haggerty, Rachel A.; Brantley, Kristen; Shibata, Etsuko; Workman, Benjamin D.; Dutta, Anindya; Varma, Dileep; Purvis, Jeremy E.; Cook, Jeanette Gowen

    2015-01-01

    Timely ubiquitin-mediated protein degradation is fundamental to cell cycle control, but the precise degradation order at each cell cycle phase transition is still unclear. We investigated the degradation order among substrates of a single human E3 ubiquitin ligase, CRL4Cdt2, which mediates the S-phase degradation of key cell cycle proteins, including Cdt1, PR-Set7, and p21. Our analysis of synchronized cells and asynchronously proliferating live single cells revealed a consistent order of replication-coupled destruction during both S-phase entry and DNA repair; Cdt1 is destroyed first, whereas p21 destruction is always substantially later than that of Cdt1. These differences are attributable to the CRL4Cdt2 targeting motif known as the PIP degron, which binds DNA-loaded proliferating cell nuclear antigen (PCNADNA) and recruits CRL4Cdt2. Fusing Cdt1's PIP degron to p21 causes p21 to be destroyed nearly concurrently with Cdt1 rather than consecutively. This accelerated degradation conferred by the Cdt1 PIP degron is accompanied by more effective Cdt2 recruitment by Cdt1 even though p21 has higher affinity for PCNADNA. Importantly, cells with artificially accelerated p21 degradation display evidence of stalled replication in mid-S phase and sensitivity to replication arrest. We therefore propose that sequential degradation ensures orderly S-phase progression to avoid replication stress and genome instability. PMID:26272819

  7. SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome.

    PubMed

    Janer, Alexandre; Prudent, Julien; Paupe, Vincent; Fahiminiya, Somayyeh; Majewski, Jacek; Sgarioto, Nicolas; Des Rosiers, Christine; Forest, Anik; Lin, Zhen-Yuan; Gingras, Anne-Claude; Mitchell, Grant; McBride, Heidi M; Shoubridge, Eric A

    2016-09-01

    Mitochondria form a dynamic network that responds to physiological signals and metabolic stresses by altering the balance between fusion and fission. Mitochondrial fusion is orchestrated by conserved GTPases MFN1/2 and OPA1, a process coordinated in yeast by Ugo1, a mitochondrial metabolite carrier family protein. We uncovered a homozygous missense mutation in SLC25A46, the mammalian orthologue of Ugo1, in a subject with Leigh syndrome. SLC25A46 is an integral outer membrane protein that interacts with MFN2, OPA1, and the mitochondrial contact site and cristae organizing system (MICOS) complex. The subject mutation destabilizes the protein, leading to mitochondrial hyperfusion, alterations in endoplasmic reticulum (ER) morphology, impaired cellular respiration, and premature cellular senescence. The MICOS complex is disrupted in subject fibroblasts, resulting in strikingly abnormal mitochondrial architecture, with markedly shortened cristae. SLC25A46 also interacts with the ER membrane protein complex EMC, and phospholipid composition is altered in subject mitochondria. These results show that SLC25A46 plays a role in a mitochondrial/ER pathway that facilitates lipid transfer, and link altered mitochondrial dynamics to early-onset neurodegenerative disease and cell fate decisions. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  8. Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair.

    PubMed

    Murgia, Claudio; Caporale, Marco; Ceesay, Ousman; Di Francesco, Gabriella; Ferri, Nicola; Varasano, Vincenzo; de las Heras, Marcelo; Palmarini, Massimo

    2011-03-01

    Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.

  9. Proline-coated column for the capillary electrochromatographic separation of amino acids by in-column derivatization.

    PubMed

    Lin, Chun-Chi; Liu, Chuen-Ying

    2004-10-01

    With 3-trimethoxysilylpropyl chloride as the spacer, a proline-coated capillary column was prepared for the capillary electrochromatographic (CEC) separation of amino acids by in-column derivatization. Nine standard mixtures, including aspartic acid, glutamic acid, valine, phenylalanine, alanine, isoleucine, leucine, tyrosine, and tryptophan, were injected. o-Phthalaldehyde (OPA), OPA/2-mercaptoethanol (2-ME) and OPA/N-acetylcysteine (NAC) in borate buffer were tested as the derivatizing agent. Among them, OPA (50 mM) in borate buffer (pH 9.5, 50 mM) gave the best performance. The formation of isoindole could be detected by UV detection. The sandwich-type injection was carried out in hydrostatic mode (10 cm) with the program R(10 s)S(10 s) R(10 s)W(10 min) with R, S, and W being the reagent, sample, and waiting times. Mesityl oxide, benzyl alcohol, and acetone showed some interaction with the column. A current monitoring method was used instead of the determination of the electroosmotic flow (EOF). The direction of EOF was from anode to cathode even under acidic condition lower than the pI value (6.31) of the bonded group due to some unreacted silanol groups. Some parameters including pH, nature, and concentration of the mobile phase and the effect of organic modifier with regard to the CEC separation were investigated. With the proline-coated column (75 (50) cm x 75 microm ID) the best separation was performed in phosphate buffer (pH 4.00, 100 mM) with an applied voltage of -15 kV. The established method was also compared with those precolumn derivatized prior to the separation with proline-coated column as well as with in-capillary derivatization and separation with a bare fused-silica column. Copyright 2004 WILEY-VCH Verlag GmbH & Co.

  10. Genetic diversity of Palestine landraces of faba bean (Vicia faba) based on RAPD markers.

    PubMed

    Basheer-Salimia, R; Shtaya, M; Awad, M; Abdallah, J; Hamdan, Y

    2013-09-03

    Until now, neither phenotypic nor molecular approaches have been used to characterize the landraces of Palestine faba beans (Vicia faba). We used PCR-based RAPD markers to determine the genetic diversity and relatedness among 26 Palestinian faba bean landraces (traditional farmers' varieties) from 8 localities in the West Bank, Palestine. In tests with 37 primers, 14 generated no polymorphic bands, 12 exhibited weak and unclear products, and 11 primers produced good amplification products with high intensity and pattern stability. Ninety-four DNA fragments (loci) were detected, with an average of 8.54 loci per primer and size ranging from 160 to 1370 bp. A minimum of 4 and a maximum of 14 DNA fragments were obtained using (OPA-05 and OPA-09) and (BC-261) primers, respectively. The maximum percentage of polymorphic markers was 71.4 (BC-298) and the minimum was 50.0 (OPA-05, -09, -16). The 11 primers exhibited relatively high collective resolving power (Rp) values of 26.316, and varied from 0.154 for the OPA-09 primer to 5.236 for the BC-261, with an overall mean of 2.392. The primers BC-261, -322, and -298 were found to be the most useful RAPD primers to assess the genetic diversity of Palestinian faba beans, as they revealed relatively high Rp rates (5.236, 3.618, and 3.150, respectively). Based on the Jaccard coefficient, the genetic distance ranged from 0.358 to 0.069, with a mean of 0.213. We conclude that the RAPD technique is useful for determining genetic diversity and for developing suitable fingerprints for faba bean landraces grown in Palestine.

  11. 2016 Workplace and Gender Relations Survey of Active Duty Members: Statistical Methodology Report

    DTIC Science & Technology

    2017-03-01

    2016 Workplace and Gender Relations Survey of Active Duty Members Statistical Methodology Report Additional copies of this report may be...MEMBERS: STATISTICAL METHODOLOGY REPORT Office of People Analytics (OPA) Defense Research, Surveys, and Statistics Center 4800 Mark Center Drive...20 1 2016 WORKPLACE AND GENDER RELATIONS SURVEY OF ACTIVE DUTY MEMBERS: STATISTICAL METHODOLOGY REPORT

  12. Three Dimensionally Interconnected Silicon Nanomembranes for Optical Phased Array (OPA) and Optical True Time Delay (TTD) Applications

    DTIC Science & Technology

    2012-06-01

    Nanophotonic Waveguides," J. Lightwave Technol. 25 (1), 151-156 (2007). [7-4] Yongbo Tang, Zhechao Wang, Lech Wosinski, Urban Westergren, and Sailing...Waveguides," Photonics Journal, IEEE 3 (2), 203-208 (2011). [8-25] Zhechao Wang, Ning Zhu, Yongbo Tang, Lech Wosinski, Daoxin Dai, and Sailing He

  13. Laparoscopic vs open approach for transverse colon cancer. A systematic review and meta-analysis of short and long term outcomes.

    PubMed

    Athanasiou, Christos D; Robinson, Jonathan; Yiasemidou, Marina; Lockwood, Sonia; Markides, Georgios A

    2017-05-01

    Transverse colon malignancies have been excluded from all randomized controlled trials comparing laparoscopic against open colectomies, potentially due to the advanced laparoscopic skills required for dissecting around the middle colic vessels and the associated morbidity. Concerns have been expressed that the laparoscopic approach may compromise the oncological clearance in transverse colon cancer. This study aimed to comprehensively compare the laparoscopic (LPA) to the open (OPA) approach by performing a meta-analysis of long and short term outcomes. Medline, Embase, Cochrane library, Scopus and Web of Knowledge databases were interrogated. Selected studies were critically appraised and the short-term morbidity and long term oncological outcomes were meta-analyzed. Sensitivity analysis according to the quality of the study, type of procedure (laparoscopic vs laparoscopically assisted) and level of lymphadenectomy was performed. Statistical heterogeneity and publication bias were also investigated. Eleven case control trials (1415 patients) were included in the study. There was no difference between the LPA and the OPA in overall survival [Hazard Ratio (HR) = 0.83 (0.56, 1.22); P = 0.34], disease free survival (p = 0.20), local recurrence (p = 0.81) or distant metastases (p = 0.24). LPA was found to have longer operative time [Weighted mean difference (WMD) = 45.00 (29.48, 60.52); P < 0.00001] with earlier establishment of oral intake [WMD = -1.68 (-1.84, -1.53); P < 0.00001] and shorter hospital stay [WMD = -2.94 (-4.27, -1.62); P = 0.0001]. No difference was found in relation to anastomotic leakage (p = 0.39), intra-abdominal abscess (p = 0.25), lymph nodes harvested (p = 0.17). LPA seems to be safe with equivalent oncological outcomes to OPA and better short term outcomes in selected patient populations. High quality Randomized control trials are required to further investigate the role of laparoscopy in transverse colon cancer. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  14. Negative affect and smoking motives sequentially mediate the effect of panic attacks on tobacco-relevant processes

    PubMed Central

    Farris, Samantha G.; Zvolensky, Michael J.; Blalock, Janice A.; Schmidt, Norman B.

    2018-01-01

    Introduction Empirical work has documented a robust and consistent relation between panic attacks and smoking behavior. Theoretical models posit smokers with panic attacks may rely on smoking to help them manage chronically elevated negative affect due to uncomfortable bodily states, which may explain higher levels of nicotine dependence and quit problems. Methods The current study examined the effects of panic attack history on nicotine dependence, perceived barriers for quitting, smoking inflexibility when emotionally distressed, and expired carbon monoxide among 461 treatment-seeking smokers. A multiple mediator path model was evaluated to examine the indirect effects of negative affect and negative affect reduction motives as mediators of the panic attack-smoking relations. Results Panic attack history was indirectly related to greater levels of nicotine dependence (b=0.039, CI95%=0.008, 0.097), perceived barriers to smoking cessation (b=0.195, CI95%=0.043, 0.479), smoking inflexibility/avoidance when emotionally distressed (b=0.188, CI95%=0.041, 0.445), and higher levels of expired carbon monoxide (b=0.071, CI95%=0.010, 0.230) through the sequential effects of negative affect and negative affect smoking motives. Conclusions The present results provide empirical support for the sequential mediating role of negative affect and smoking motives for negative affect reduction in the relation between panic attacks and a variety of smoking variables in treatment-seeking smokers. These mediating variables are likely important processes to address in smoking cessation treatment, especially in panic-vulnerable smokers. PMID:24720260

  15. Negative affect and smoking motives sequentially mediate the effect of panic attacks on tobacco-relevant processes.

    PubMed

    Farris, Samantha G; Zvolensky, Michael J; Blalock, Janice A; Schmidt, Norman B

    2014-05-01

    Empirical work has documented a robust and consistent relation between panic attacks and smoking behavior. Theoretical models posit smokers with panic attacks may rely on smoking to help them manage chronically elevated negative affect due to uncomfortable bodily states, which may explain higher levels of nicotine dependence and quit problems. The current study examined the effects of panic attack history on nicotine dependence, perceived barriers for quitting, smoking inflexibility when emotionally distressed, and expired carbon monoxide among 461 treatment-seeking smokers. A multiple mediator path model was evaluated to examine the indirect effects of negative affect and negative affect reduction motives as mediators of the panic attack-smoking relations. Panic attack history was indirectly related to greater levels of nicotine dependence (b = 0.039, CI95% = 0.008, 0.097), perceived barriers to smoking cessation (b = 0.195, CI95% = 0.043, 0.479), smoking inflexibility/avoidance when emotionally distressed (b = 0.188, CI95% = 0.041, 0.445), and higher levels of expired carbon monoxide (b = 0.071, CI95% = 0.010, 0.230) through the sequential effects of negative affect and negative affect smoking motives. The present results provide empirical support for the sequential mediating role of negative affect and smoking motives for negative affect reduction in the relation between panic attacks and a variety of smoking variables in treatment-seeking smokers. These mediating variables are likely important processes to address in smoking cessation treatment, especially in panic-vulnerable smokers.

  16. Scattering and Polarization Measurements Using the PL/OPA Low Altitude Lidar

    DTIC Science & Technology

    1990-12-20

    66 A.3.2 Application to Lidar Data .. .. .. .. .. ... ... ... .. 70 References 72 iv List of Figures 1 The Poincare ... the vcctor in the I __ plane is the degree of linear polarization (defined as [Q2 + U2 II/2 /1). The component of the vector along the K axis is the ...scattering refers to the scattering of a monochromatic electromagr1tic plane wave by a spherically shaped, homogeneous, isotropic dielectric and conducting

  17. Do material, psychosocial and behavioural factors mediate the relationship between disability acquisition and mental health? A sequential causal mediation analysis.

    PubMed

    Aitken, Zoe; Simpson, Julie Anne; Gurrin, Lyle; Bentley, Rebecca; Kavanagh, Anne Marie

    2018-01-29

    There is evidence of a causal relationship between disability acquisition and poor mental health; however, the mechanism by which disability affects mental health is poorly understood. This gap in understanding limits the development of effective interventions to improve the mental health of people with disabilities. We used four waves of data from the Household, Income and Labour Dynamics in Australia Survey (2011-14) to compare self-reported mental health between individuals who acquired any disability (n=387) and those who remained disability-free (n=7936). We tested three possible pathways from disability acquisition to mental health, examining the effect of material, psychosocial and behavioural mediators. The effect was partitioned into natural direct and indirect effects through the mediators using a sequential causal mediation analysis approach. Multiple imputation using chained equations was used to assess the impact of missing data. Disability acquisition was estimated to cause a five-point decline in mental health [estimated mean difference: -5.3, 95% confidence interval (CI) -6.8, -3.7]. The indirect effect through material factors was estimated to be a 1.7-point difference (-1.7, 95% CI -2.8, -0.6), explaining 32% of the total effect, with a negligible proportion of the effect explained by the addition of psychosocial characteristics (material and psychosocial: -1.7, 95% CI -3.0, -0.5) and a further 5% by behavioural factors (material-psychosocial-behavioural: -2.0, 95% CI -3.4, -0.6). The finding that the effect of disability acquisition on mental health operates predominantly through material rather than psychosocial and behavioural factors has important implications. The results highlight the need for better social protection, including income support, employment and education opportunities, and affordable housing for people who acquire a disability. © The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  18. Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8

    PubMed Central

    Adrian, Nicole; Siebenborn, Uta; Fadle, Natalie; Plesko, Margarita; Fischer, Eliane; Wüest, Thomas; Stenner, Frank; Mertens, Joachim C.; Knuth, Alexander; Ritter, Gerd; Old, Lloyd J.; Renner, Christoph

    2009-01-01

    Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-mediated chemotactic response, we generated immunocytokines by N-terminal fusion of a human anti-FAP scFv fragment with human IL-8 (IL-872) and its N-terminally truncated form IL-83-72. Due to the dramatic difference in chemotaxis induction in vitro, we favored the mature chemokine fused to the anti-FAP scFv for further investigation in vivo. BALB/c nu/nu mice were simultaneously xenografted with FAP-positive or -negative tumors and extended chemo-attraction of PMNs was only detectable in FAP-expressing tissue after intravenous administration of the anti-FAP scFv-IL-872 construct. As TNF-activated PMNs are likewise producers and primary targets for IL-8, we investigated the therapeutic efficacy of co-administration of both effectors: Sequential application of scFv-IL-872 and dimeric IgG1-TNF fusion proteins significantly enhanced anti-tumor activity when compared either to a single effector treatment regimen or sequential application of non-targeted cytokines, indicating that the tumor-restricted sequential application of IL-872 and TNF is a promising approach for cancer therapy. PMID:19267427

  19. Occupational physical activity assessment for chronic disease prevention and management: A review of methods for both occupational health practitioners and researchers.

    PubMed

    Scott, Kenneth A; Browning, Raymond C

    2016-01-01

    Occupational physical activity (OPA) is an occupational exposure that impacts worker health. OPA is amenable to measurement and modification through the hierarchy of controls. Occupational exposure scientists have roles in addressing inadequate physical activity, as well as excessive or harmful physical activity. Occupational health researchers can contribute to the development of novel OPA exposure assessment techniques and to epidemiologic studies examining the health impacts of physical activity at work. Occupational health practitioners stand to benefit from understanding the strengths and limitations of physical activity measurement approaches, such as accelerometers in smartphones, which are already ubiquitous in many workplaces and in some worksite health programs. This comprehensive review of the literature provides an overview of physical activity monitoring for occupational exposure scientists. This article summarizes data on the public health implications of physical activity at work, highlighting complex relationships with common chronic diseases. This article includes descriptions of several techniques that have been used to measure physical activity at work and elsewhere, focusing in detail on pedometers, accelerometers, and Global Positioning System technology. Additional subjective and objective measurement strategies are described as well.

  20. Three-Dimensions vs. Two-Dimensions Intervention Programs: The Effect on the Mediation Level and Behavioural Aspects of Children with Intellectual Disability

    ERIC Educational Resources Information Center

    Eden, S.; Bezer, M.

    2011-01-01

    The research examined the effect of an intervention program employing 3D immersive virtual reality (IVR), which focused on the perception of sequential time, on the mediation level and behavioural aspects of children with intellectual disability (ID). The intervention is based on the mediated learning experience (MLE) theory, which refers the…

  1. High-performance liquid chromatography - Ultraviolet method for the determination of total specific migration of nine ultraviolet absorbers in food simulants based on 1,1,3,3-Tetramethylguanidine and organic phase anion exchange solid phase extraction to remove glyceride.

    PubMed

    Wang, Jianling; Xiao, Xiaofeng; Chen, Tong; Liu, Tingfei; Tao, Huaming; He, Jun

    2016-06-17

    The glyceride in oil food simulant usually causes serious interferences to target analytes and leads to failure of the normal function of the RP-HPLC column. In this work, a convenient HPLC-UV method for the determination of the total specific migration of nine ultraviolet (UV) absorbers in food simulants was developed based on 1,1,3,3-tetramethylguanidine (TMG) and organic phase anion exchange (OPAE) SPE to efficiently remove glyceride in olive oil simulant. In contrast to the normal ion exchange carried out in an aqueous solution or aqueous phase environment, the OPAE SPE was performed in the organic phase environments, and the time-consuming and challenging extraction of the nine UV absorbers from vegetable oil with aqueous solution could be readily omitted. The method was proved to have good linearity (r≥0.99992), precision (intra-day RSD≤3.3%), and accuracy(91.0%≤recoveries≤107%); furthermore, the lower limit of quantifications (0.05-0.2mg/kg) in five types of food simulants(10% ethanol, 3% acetic acid, 20% ethanol, 50% ethanol and olive oil) was observed. The method was found to be well suited for quantitative determination of the total specific migration of the nine UV absorbers both in aqueous and vegetable oil simulant according to Commission Regulation (EU) No. 10/2011. Migration levels of the nine UV absorbers were determined in 31 plastic samples, and UV-24, UV-531, HHBP and UV-326 were frequently detected, especially in olive oil simulant for UV-326 in PE samples. In addition, the OPAE SPE procedure was also been applied to efficiently enrich or purify seven antioxidants in olive oil simulant. Results indicate that this procedure will have more extensive applications in the enriching or purification of the extremely weak acidic compounds with phenol hydroxyl group that are relatively stable in TMG n-hexane solution and that can be barely extracted from vegetable oil. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds.

    PubMed

    Kitao, Kyoko; Mutai, Hideki; Namba, Kazunori; Morimoto, Noriko; Nakano, Atsuko; Arimoto, Yukiko; Sugiuchi, Tomoko; Masuda, Sawako; Okamoto, Yasuhide; Morita, Noriko; Sakamoto, Hirokazu; Shintani, Tomoko; Fukuda, Satoshi; Kaga, Kimitaka; Matsunaga, Tatsuo

    2018-04-23

    Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions. The purpose of this study was to investigate the time course of changes in distortion product otoacoustic emissions (DPOAEs) in association with patients' genetic and clinical backgrounds, including the use of hearing aids. DPOAE measurements from 31 patients with AN were assessed. Genetic analyses for GJB2, OTOF, and mitochondrial m.1555A> G and m.3243A> G mutations were conducted for all cases, and the analyses for CDH23 and OPA1 were conducted for the selected cases. Patients who were younger than 10 years of age at the time of AN diagnosis were designated as the pediatric AN group (22 cases), and those who were 18 years of age or older were designated as the adult AN group (9 cases). DPOAE was measured at least twice in all patients. The response rate for DPOAEs was defined and analyzed. The pediatric AN group comprised 10 patients with OTOF mutations, 1 with GJB2 mutations, 1 with OPA1 mutation, and 10 with indefinite causes. Twelve ears (27%) showed no change in DPOAE, 20 ears (46%) showed a decrease in DPOAE, and 12 ears (27%) lost DPOAE. Loss of DPOAE occurred in one ear (2%) at 0 years of age and four ears (9%) at 1 year of age. The time courses of DPOAEs in patients with OTOF mutations were divided into those with early loss and those with no change, indicating that the mechanism for deterioration of DPOAEs includes not only the OTOF mutations but also other common modifier factors. Most, but not all, AN patients who used hearing aids showed deterioration of DPOAEs after the start of using hearing aids. A few AN patients also showed deterioration of DPOAEs before using hearing aids. The adult AN group comprised 2 patients with OPA1 mutations, 2 with OTOF mutations, and 5 with indefinite causes. Four ears (22%) showed no change in DPOAE, 13 ears (72%) showed a decrease, and one ear (6%) showed a loss of DPOAE. Although the ratio of DPOAE decrease was higher in the adult AN group than in the pediatric AN group, the ratio of DPOAE loss was lower in the adult AN group. DPOAE was not lost in all four ears with OPA1 mutations and in all four ears with OTOF mutations in the adult group. DPOAE was decreased or lost in approximately 70% of pediatric and about 80% of adult AN patients. Eleven percent of pediatric AN patients lost DPOAEs by 1 year of age. Genetic factors were thought to have influenced the time course of DPOAEs in the pediatric AN group. In most adult AN patients, DPOAE was rarely lost regardless of the genetic cause.

  3. Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants.

    PubMed

    Knuf, Markus; Pankow-Culot, Heidemarie; Grunert, Detlef; Rapp, Michael; Panzer, Falko; Köllges, Ralph; Fanic, Aurélie; Habib, Ahsan; Borys, Dorota; Dieussaert, Ilse; Schuerman, Lode

    2012-01-01

    Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.

  4. Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis

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

    Carnevale, Francisco C., E-mail: fcarnevale@uol.com.br; Iscaife, Alexandre, E-mail: iscaifeboni@yahoo.com.br; Yoshinaga, Eduardo M., E-mail: dumuracca@ig.com.br

    PurposeTo compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia.MethodsWe prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL).ResultsAll groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q{sub max}), both of which were significantly better in the TURP group,more » and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q{sub max}. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q{sub max} and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria.ConclusionsTURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.« less

  5. Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.

    PubMed

    Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

    2015-01-01

    This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.

  6. Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study

    PubMed Central

    Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

    2015-01-01

    This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3–4–5 months of age) and booster vaccination (17–19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children. PMID:25830489

  7. Impact of temporal, spatial and cascaded effects on the pulse formation in ultra-broadband parametric amplifiers.

    PubMed

    Lang, T; Harth, A; Matyschok, J; Binhammer, T; Schultze, M; Morgner, U

    2013-01-14

    A 2 + 1 dimensional nonlinear pulse propagation model is presented, illustrating the weighting of different effects for the parametric amplification of ultra-broadband spectra in different regimes of energy scaling. Typical features in the distribution of intensity and phase of state-of-the-art OPA-systems can be understood by cascaded spatial and temporal effects.

  8. Development of a simple fluorescence-based microplate method for the high-throughput analysis of proline in wine samples.

    PubMed

    Robert-Peillard, Fabien; Boudenne, Jean-Luc; Coulomb, Bruno

    2014-05-01

    This paper presents a simple, accurate and multi-sample method for the determination of proline in wines thanks to a 96-well microplate technique. Proline is the most abundant amino acid in wine and is an important parameter related to wine characteristics or maturation processes of grape. In the current study, an improved application of the general method based on sodium hypochlorite oxidation and o-phthaldialdehyde (OPA)-thiol spectrofluorometric detection is described. The main interfering compounds for specific proline detection in wines are strongly reduced by selective reaction with OPA in a preliminary step under well-defined pH conditions. Application of the protocol after a 500-fold dilution of wine samples provides a working range between 0.02 and 2.90gL(-1), with a limit of detection of 7.50mgL(-1). Comparison and validation on real wine samples by ion-exchange chromatography prove that this procedure yields accurate results. Simplicity of the protocol used, with no need for centrifugation or filtration, organic solvents or high temperature enables its full implementation in plastic microplates and efficient application for routine analysis of proline in wines. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Executive function skills and academic achievement gains in prekindergarten: Contributions of learning-related behaviors.

    PubMed

    Nesbitt, Kimberly Turner; Farran, Dale Clark; Fuhs, Mary Wagner

    2015-07-01

    Although research suggests associations between children's executive function skills and their academic achievement, the specific mechanisms that may help explain these associations in early childhood are unclear. This study examined whether children's (N = 1,103; M age = 54.5 months) executive function skills at the beginning of prekindergarten (pre-K) predict their learning-related behaviors in the classroom and whether these behaviors then mediate associations between children's executive function skills and their pre-K literacy, language, and mathematic gains. Learning-related behaviors were quantified in terms of (a) higher levels of involvement in learning opportunities; (b) greater frequency of participation in activities that require sequential steps; (c) more participation in social-learning interactions; and (d) less instances of being unoccupied, disruptive, or in time out. Results indicated that children's learning-related behaviors mediated associations between executive function skills and literacy and mathematics gains through children's level of involvement, sequential learning behaviors, and disengagement from the classroom. The implications of the findings for early childhood education are discussed. (c) 2015 APA, all rights reserved).

  10. Ozone-initiated terpene reaction products in five European offices: replacement of a floor cleaning agent.

    PubMed

    Nørgaard, A W; Kofoed-Sørensen, V; Mandin, C; Ventura, G; Mabilia, R; Perreca, E; Cattaneo, A; Spinazzè, A; Mihucz, V G; Szigeti, T; de Kluizenaar, Y; Cornelissen, H J M; Trantallidi, M; Carrer, P; Sakellaris, I; Bartzis, J; Wolkoff, P

    2014-11-18

    Cleaning agents often emit terpenes that react rapidly with ozone. These ozone-initiated reactions, which occur in the gas-phase and on surfaces, produce a host of gaseous and particulate oxygenated compounds with possible adverse health effects in the eyes and airways. Within the European Union (EU) project OFFICAIR, common ozone-initiated reaction products were measured before and after the replacement of the regular floor cleaning agent with a preselected low emitting floor cleaning agent in four offices located in four EU countries. One reference office in a fifth country did not use any floor cleaning agent. Limonene, α-pinene, 3-carene, dihydromyrcenol, geraniol, linalool, and α-terpineol were targeted for measurement together with the common terpene oxidation products formaldehyde, 4-acetyl-1-methylcyclohexene (4-AMCH), 3-isopropenyl-6-oxo-heptanal (IPOH), 6-methyl-5-heptene-2-one, (6-MHO), 4-oxopentanal (4-OPA), and dihydrocarvone (DHC). Two-hour air samples on Tenax TA and DNPH cartridges were taken in the morning, noon, and in the afternoon and analyzed by thermal desorption combined with gas chromatography/mass spectrometry and HPLC/UV analysis, respectively. Ozone was measured in all sites. All the regular cleaning agents emitted terpenes, mainly limonene and linalool. After the replacement of the cleaning agent, substantially lower concentrations of limonene and formaldehyde were observed. Some of the oxidation product concentrations, in particular that of 4-OPA, were also reduced in line with limonene. Maximum 2 h averaged concentrations of formaldehyde, 4-AMCH, 6-MHO, and IPOH would not give rise to acute eye irritation-related symptoms in office workers; similarly, 6-AMCH, DHC and 4-OPA would not result in airflow limitation to the airways.

  11. Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence: A Putative Mechanistic Neurodevelopmental Pathway.

    PubMed

    Luby, Joan L; Barch, Deanna; Whalen, Diana; Tillman, Rebecca; Belden, Andy

    2017-12-01

    Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood. To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes. A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit. Early life adversity. Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years. The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively. Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

  12. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

    PubMed Central

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-01-01

    ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

  13. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

    PubMed

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-08-02

    Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

  14. ARF1 and SAR1 GTPases in Endomembrane Trafficking in Plants

    PubMed Central

    Cevher-Keskin, Birsen

    2013-01-01

    Small GTPases largely control membrane traffic, which is essential for the survival of all eukaryotes. Among the small GTP-binding proteins, ARF1 (ADP-ribosylation factor 1) and SAR1 (Secretion-Associated RAS super family 1) are commonly conserved among all eukaryotes with respect to both their functional and sequential characteristics. The ARF1 and SAR1 GTP-binding proteins are involved in the formation and budding of vesicles throughout plant endomembrane systems. ARF1 has been shown to play a critical role in COPI (Coat Protein Complex I)-mediated retrograde trafficking in eukaryotic systems, whereas SAR1 GTPases are involved in intracellular COPII-mediated protein trafficking from the ER to the Golgi apparatus. This review offers a summary of vesicular trafficking with an emphasis on the ARF1 and SAR1 expression patterns at early growth stages and in the de-etiolation process. PMID:24013371

  15. Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from Streptococcus gordonii

    PubMed Central

    Chen, Yu; Bensing, Barbara A.; Seepersaud, Ravin; Mi, Wei; Liao, Maofu; Jeffrey, Philip D.; Shajahan, Asif; Sonon, Roberto N.; Azadi, Parastoo; Sullam, Paul M.; Rapoport, Tom A.

    2018-01-01

    Many pathogenic bacteria, including Streptococcus gordonii, possess a pathway for the cellular export of a single serine-rich-repeat protein that mediates the adhesion of bacteria to host cells and the extracellular matrix. This adhesin protein is O-glycosylated by several cytosolic glycosyltransferases and requires three accessory Sec proteins (Asp1–3) for export, but how the adhesin protein is processed for export is not well understood. Here, we report that the S. gordonii adhesin GspB is sequentially O-glycosylated by three enzymes (GtfA/B, Nss, and Gly) that attach N-acetylglucosamine and glucose to Ser/Thr residues. We also found that modified GspB is transferred from the last glycosyltransferase to the Asp1/2/3 complex. Crystal structures revealed that both Asp1 and Asp3 are related to carbohydrate-binding proteins, suggesting that they interact with carbohydrates and bind glycosylated adhesin, a notion that was supported by further analyses. We further observed that Asp1 also has an affinity for phospholipids, which is attenuated by Asp2. In summary, our findings support a model in which the GspB adhesin is sequentially glycosylated by GtfA/B, Nss, and Gly and then transferred to the Asp1/2/3 complex in which Asp1 mediates the interaction of the Asp1/2/3 complex with the lipid bilayer for targeting of matured GspB to the export machinery. PMID:29462788

  16. Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from Streptococcus gordonii.

    PubMed

    Chen, Yu; Bensing, Barbara A; Seepersaud, Ravin; Mi, Wei; Liao, Maofu; Jeffrey, Philip D; Shajahan, Asif; Sonon, Roberto N; Azadi, Parastoo; Sullam, Paul M; Rapoport, Tom A

    2018-04-06

    Many pathogenic bacteria, including Streptococcus gordonii , possess a pathway for the cellular export of a single serine-rich-repeat protein that mediates the adhesion of bacteria to host cells and the extracellular matrix. This adhesin protein is O -glycosylated by several cytosolic glycosyltransferases and requires three accessory Sec proteins (Asp1-3) for export, but how the adhesin protein is processed for export is not well understood. Here, we report that the S. gordonii adhesin GspB is sequentially O -glycosylated by three enzymes (GtfA/B, Nss, and Gly) that attach N -acetylglucosamine and glucose to Ser/Thr residues. We also found that modified GspB is transferred from the last glycosyltransferase to the Asp1/2/3 complex. Crystal structures revealed that both Asp1 and Asp3 are related to carbohydrate-binding proteins, suggesting that they interact with carbohydrates and bind glycosylated adhesin, a notion that was supported by further analyses. We further observed that Asp1 also has an affinity for phospholipids, which is attenuated by Asp2. In summary, our findings support a model in which the GspB adhesin is sequentially glycosylated by GtfA/B, Nss, and Gly and then transferred to the Asp1/2/3 complex in which Asp1 mediates the interaction of the Asp1/2/3 complex with the lipid bilayer for targeting of matured GspB to the export machinery.

  17. Noiseless optical amplification in quasi-phase-matched bulk lithium niobate

    NASA Astrophysics Data System (ADS)

    Lovering, D. J.; Levenson, J. A.; Vidakovic, P.; Webjörn, J.; Russell, P. St. J.

    1996-09-01

    An optical parametric amplifier (OPA) has been demonstrated in bulk, periodically poled lithium niobate and is shown to operate with a noise figure well below the classical limit. In contrast to conventional OPA's, this device uses quasi-phase matching to provide the coupling between the pump and the signal. Comparison of the measured performance with that of a theoretical model reveals that the main intrinsic contribution to the output noise is due to spatial and temporal mode mixing, which arises as a consequence of tight focusing of the incident beams. Factors that affect the performance of this amplifier are identified theoretically and their relative importance investigated for both amplification and squeezing.

  18. HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition.

    PubMed

    Fiorini, Francesca; Robin, Jean-Philippe; Kanaan, Joanne; Borowiak, Malgorzata; Croquette, Vincent; Le Hir, Hervé; Jalinot, Pierre; Mocquet, Vincent

    2018-01-30

    Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome.

  19. Toward a Better Understanding of Student Perceptions of Writing Feedback: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Zumbrunn, Sharon; Marrs, Sarah; Mewborn, Caitlin

    2016-01-01

    This explanatory sequential mixed methods study investigated the writing feedback perceptions of middle and high school students (N = 598). The predictive and mediational roles of writing self-efficacy and perceptions of writing feedback on student writing self-regulation aptitude were examined using mediation regression analysis. To augment the…

  20. Quasi-supercontinuum source in the extreme ultraviolet using multiple frequency combs from high-harmonic generation

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

    Wünsche, Martin; Fuchs, Silvio; Aull, Stefan

    A quasi-supercontinuum source in the extreme ultraviolet (XUV) is demonstrated using a table-top femtosecond laser and a tunable optical parametric amplifier (OPA) as a driver for high-harmonic generation (HHG). The harmonic radiation, which is usually a comb of odd multiples of the fundamental frequency, is generated by near-infrared (NIR) laser pulses from the OPA. A quasi-continuous XUV spectrum in the range of 30 to 100 eV is realized by averaging over multiple harmonic comb spectra with slightly different fundamental frequencies and thus different spectral spacing between the individual harmonics. The driving laser wavelength is swept automatically during an averaging timemore » period. With a total photon flux of 4×10 9 photons/s in the range of 30 eV to 100 eV and 1×10 7 photons/s in the range of 100 eV to 200 eV, the resulting quasi-supercontinuum XUV source is suited for applications such as XUV coherence tomography (XCT) or near-edge absorption fine structure spectroscopy (NEXAFS).« less

  1. Quasi-supercontinuum source in the extreme ultraviolet using multiple frequency combs from high-harmonic generation

    DOE PAGES

    Wünsche, Martin; Fuchs, Silvio; Aull, Stefan; ...

    2017-03-16

    A quasi-supercontinuum source in the extreme ultraviolet (XUV) is demonstrated using a table-top femtosecond laser and a tunable optical parametric amplifier (OPA) as a driver for high-harmonic generation (HHG). The harmonic radiation, which is usually a comb of odd multiples of the fundamental frequency, is generated by near-infrared (NIR) laser pulses from the OPA. A quasi-continuous XUV spectrum in the range of 30 to 100 eV is realized by averaging over multiple harmonic comb spectra with slightly different fundamental frequencies and thus different spectral spacing between the individual harmonics. The driving laser wavelength is swept automatically during an averaging timemore » period. With a total photon flux of 4×10 9 photons/s in the range of 30 eV to 100 eV and 1×10 7 photons/s in the range of 100 eV to 200 eV, the resulting quasi-supercontinuum XUV source is suited for applications such as XUV coherence tomography (XCT) or near-edge absorption fine structure spectroscopy (NEXAFS).« less

  2. Pioneer Venus Data Analysis

    NASA Technical Reports Server (NTRS)

    Jones, Douglas E.

    1996-01-01

    Analysis and interpretation of data from the Orbiter Retarding Potential Analyzer (ORPA) onboard the Pioneer Venus Orbiter is reported. By comparing ORPA data to proton data from the Orbiter Plasma Analyzer (OPA), it was found that the ORPA suprathermal electron densities taken outside the Venusian ionopause represent solar wind electron densities, thus allowing the high resolution study of Venus bow shocks using both magnetic field and solar wind electron data. A preliminary analysis of 366 bow shock penetrations was completed using the solar wind electron data as determined from ORPA suprathermal electron densities and temperatures, resulting in an estimate of the extent to which mass loading pickup of O+ (UV ionized O atoms flowing out of the Venus atmosphere) upstream of the Venus obstacle occurred. The pickup of O+ averaged 9.95%, ranging from 0.78% to 23.63%. Detailed results are reported in two attached theses: (1) Comparison of ORPA Suprathermal Electron and OPA Solar Wind Proton Data from the Pioneer Venus Orbiter and (2) Pioneer Venus Orbiter Retarding Potential Analyzer Observations of the Electron Component of the Solar Wind, and of the Venus Bow Shock and Magnetosheath.

  3. Recruitment of mitofusin 2 into “lipid rafts” drives mitochondria fusion induced by Mdivi-1

    PubMed Central

    Ciarlo, Laura; Vona, Rosa; Manganelli, Valeria; Gambardella, Lucrezia; Raggi, Carla; Marconi, Matteo; Malorni, Walter; Sorice, Maurizio; Garofalo, Tina; Matarrese, Paola

    2018-01-01

    The regulation of the mitochondrial dynamics and the balance between fusion and fission processes are crucial for the health and fate of the cell. Mitochondrial fusion and fission machinery is controlled by key proteins such as mitofusins, OPA-1 and several further molecules. In the present work we investigated the implication of lipid rafts in mitochondrial fusion induced by Mdivi-1. Our results underscore the possible implication of lipid “rafts” in mitochondrial morphogenetic changes and their homeostasis. PMID:29721168

  4. The effect of 10% carbamide peroxide bleaching material on microhardness of sound and demineralized enamel and dentin in situ.

    PubMed

    Basting, R T; Rodrigues Júnior, A L; Serra, M C

    2001-01-01

    This in situ study evaluated the microhardness of sound and demineralized enamel and dentin submitted to treatment with 10% carbamide peroxide for three weeks. A 10% carbamide peroxide bleaching agent--Opalescence/Ultradent (OPA)--was evaluated against a placebo agent (PLA). Two hundred and forty dental fragments--60 sound enamel fragments (SE), 60 demineralized enamel fragments (DE), 60 sound dentin fragments (SD) and 60 demineralized dentin fragments (DD)--were randomly fixed on the vestibular surface of the first superior molars and second superior premolars of 30 volunteers. The volunteers were divided into two groups that received bleaching or the placebo agent at different sequences and periods at a double blind 2 x 2 crossover study with a wash-out period of two weeks. Microhardness tests were performed on the enamel and dentin surface. The SE and DE submitted to treatment with OPA showed lower microhardness values than the SE and DE submitted to treatment with PLA. There were no statistical differences in microhardness values for SD and DD submitted to the treatment with OPA and PLA. The results suggest that treatment with 10% carbamide peroxide bleaching material for three weeks alters the enamel microhardness, although it does not seem to alter the dentin microhardness.

  5. 10-year trends in physical activity in the eastern Finnish adult population: relationship to socioeconomic and lifestyle characteristics.

    PubMed

    Marti, B; Salonen, J T; Tuomilehto, J; Puska, P

    1988-01-01

    In a large, community-based cardiovascular disease prevention study in Eastern Finland, independent random population samples were surveyed in 1972, 1977 and 1982. The leisure-time physical activity (LTPA), occupational physical activity (OPA), and socioeconomic and lifestyle characteristics were assessed. In men and women aged 30-59, the proportion with high LTPA increased from 1972 to 1982 by approximately one half (p less than 0.001), whereas that of high OPA decreased during the same period (p less than 0.001). In both sexes, high overall physical activity fell from 1972 to 1977 (p less than 0.001), but no more from 1977 to 1982. The proportion of entirely sedentary remained stable. Education, income and younger age showed a positive, body mass index, smoking and OPA a graded, negative association with high LTPA in 1972 and 1982. Significant (p less than 0.001) differences in 10-year trends of changes in LTPA were observed: men and women with low education or income increased LTPA more than those with high education and income. Socioeconomic factors, such as income and education, appear to have lost importance as determinants of population-wide exercise, whereas the clustering of low physical activity with overweight and smoking has increased.

  6. 2016 Service Academy Gender Relations Survey: Overview Report

    DTIC Science & Technology

    2017-02-01

    environment within the Academies. This Executive Summary will provide a summary of the methodology used and the top line results from the survey.1 Summary...discussion of the measurement constructs, a description of the survey methodology , and detailed presentation of the results. Each report section...are determined statistically significant at an alpha (α) level of .05.6 Survey Methodology Statistical Design OPA conducts cross-Service surveys that

  7. Identity-level representations affect unfamiliar face matching performance in sequential but not simultaneous tasks.

    PubMed

    Menon, Nadia; White, David; Kemp, Richard I

    2015-01-01

    According to cognitive and neurological models of the face-processing system, faces are represented at two levels of abstraction. First, image-based pictorial representations code a particular instance of a face and include information that is unrelated to identity-such as lighting, pose, and expression. Second, at a more abstract level, identity-specific representations combine information from various encounters with a single face. Here we tested whether identity-level representations mediate unfamiliar face matching performance. Across three experiments we manipulated identity attributions to pairs of target images and measured the effect on subsequent identification decisions. Participants were instructed that target images were either two photos of the same person (1ID condition) or photos of two different people (2ID condition). This manipulation consistently affected performance in sequential matching: 1ID instructions improved accuracy on "match" trials and caused participants to adopt a more liberal response bias than the 2ID condition. However, this manipulation did not affect performance in simultaneous matching. We conclude that identity-level representations, generated in working memory, influence the amount of variation tolerated between images, when making identity judgements in sequential face matching.

  8. Association of Occupational and Leisure-Time Physical Activity with Aerobic Capacity in a Working Population.

    PubMed

    Mundwiler, Jonas; Schüpbach, Ulla; Dieterle, Thomas; Leuppi, Jörg Daniel; Schmidt-Trucksäss, Arno; Wolfer, David Paul; Miedinger, David; Brighenti-Zogg, Stefanie

    2017-01-01

    Objective data on the association of maximal aerobic capacity (VO2max) with work related physical activity are sparse. Thus, it is not clear whether occupational physical activity (OPA) contributes to an increase of VO2max. This study examined the association of VO2max with work and non-work related physical activity in a Swiss working population. In this cross-sectional study, a total of 337 healthy and full-time employed adults were recruited. Demographic data, height, weight and BMI were recorded in all subjects. Participants were classified into nine occupational categories (ISCO-88) and merged into three groups with low, moderate, and high OPA. Physical activity was objectively measured by the SenseWear Mini Armband on seven consecutive days (23 hours per day). Participants were regarded as sufficiently active when accumulating ≥30 min of moderate-to-vigorous physical activity per day. VO2max was evaluated using the multistage 20-meter shuttle run test. Data of 303 participants were considered for analysis (63% male, age 33 yrs, SD 12). Multiple linear regression analysis (adjusted R2 = 0.69) revealed significant positive associations of VO2max with leisure-time physical activity (LTPA) at vigorous intensity (β = 0.212) and sufficient moderate-to-vigorous physical activity (β = 0.100) on workdays. Female gender (β = -0.622), age (β = -0.264), BMI (β = -0.220), the ratio of maximum to resting heart rate (β = 0.192), occupational group (low vs. high OPA, β = -0.141), and smoking (β = -0.133) were also identified as independent predictors of VO2max. The present results suggest that VO2max is positively associated with LTPA, but not with OPA on workdays. This finding emphasizes the need for employees to engage in sufficient high-intensity physical activity in recreation for maintaining or improving VO2max with regard to health benefits.

  9. Association of Occupational and Leisure-Time Physical Activity with Aerobic Capacity in a Working Population

    PubMed Central

    Mundwiler, Jonas; Schüpbach, Ulla; Dieterle, Thomas; Leuppi, Jörg Daniel; Schmidt-Trucksäss, Arno; Wolfer, David Paul; Miedinger, David; Brighenti-Zogg, Stefanie

    2017-01-01

    Introduction Objective data on the association of maximal aerobic capacity (VO2max) with work related physical activity are sparse. Thus, it is not clear whether occupational physical activity (OPA) contributes to an increase of VO2max. This study examined the association of VO2max with work and non-work related physical activity in a Swiss working population. Methods In this cross-sectional study, a total of 337 healthy and full-time employed adults were recruited. Demographic data, height, weight and BMI were recorded in all subjects. Participants were classified into nine occupational categories (ISCO-88) and merged into three groups with low, moderate, and high OPA. Physical activity was objectively measured by the SenseWear Mini Armband on seven consecutive days (23 hours per day). Participants were regarded as sufficiently active when accumulating ≥30 min of moderate-to-vigorous physical activity per day. VO2max was evaluated using the multistage 20-meter shuttle run test. Results Data of 303 participants were considered for analysis (63% male, age 33 yrs, SD 12). Multiple linear regression analysis (adjusted R2 = 0.69) revealed significant positive associations of VO2max with leisure-time physical activity (LTPA) at vigorous intensity (β = 0.212) and sufficient moderate-to-vigorous physical activity (β = 0.100) on workdays. Female gender (β = -0.622), age (β = -0.264), BMI (β = -0.220), the ratio of maximum to resting heart rate (β = 0.192), occupational group (low vs. high OPA, β = -0.141), and smoking (β = -0.133) were also identified as independent predictors of VO2max. Conclusions The present results suggest that VO2max is positively associated with LTPA, but not with OPA on workdays. This finding emphasizes the need for employees to engage in sufficient high-intensity physical activity in recreation for maintaining or improving VO2max with regard to health benefits. PMID:28045939

  10. A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle.

    PubMed

    Linke, Christian; Chasapi, Anastasia; González-Novo, Alberto; Al Sawad, Istabrak; Tognetti, Silvia; Klipp, Edda; Loog, Mart; Krobitsch, Sylvia; Posas, Francesc; Xenarios, Ioannis; Barberis, Matteo

    2017-01-01

    Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression. Experimental validation highlights Fkh2 as modulator of CLB3 transcript levels, besides its role in regulating CLB2 expression. A Boolean model based on the minimal number of interactions needed to capture the information flow of the Clb/Cdk1 network supports the role of an activator molecule in the sequential activation, and oscillatory behavior, of mitotic Clb cyclins. This work illustrates how transcription and phosphorylation networks can be coupled by a Clb/Cdk1-mediated regulation that synchronizes them.

  11. Mitochondrial dynamics in mammalian health and disease.

    PubMed

    Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

    2009-07-01

    The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.

  12. The Long-Term Effectiveness of the Family Check-up on Peer Preference: Parent-Child Interaction and Child Effortful Control as Sequential Mediators.

    PubMed

    Chang, Hyein; Shaw, Daniel S; Shelleby, Elizabeth C; Dishion, Thomas J; Wilson, Melvin N

    2017-05-01

    We examined the longitudinal effects of the Family Check-Up (FCU) intervention beginning in toddlerhood on children's peer preference at school-age. Specifically, a sequential mediational model was proposed in which the FCU was hypothesized to promote peer preference (i.e., higher acceptance and lower rejection by peers) in middle childhood through its positive effects on parent-child interaction and child effortful control in early childhood. Participants were 731 low-income families (49 % female). Qualities of parent-child interaction were observed during structured activities at 2 to 5 years, child effortful control was assessed using behavioral tasks at 5 years, and peer acceptance and rejection were rated by teachers at 7.5 to 10.5 years. Results indicated that the FCU indirectly predicted peer preference by sequentially improving parent-child interaction and child effortful control. The findings are discussed with respect to implications for understanding mechanisms by which early parenting-focused programs may enhance child functioning across time and context.

  13. The Long-Term Effectiveness of the Family Check-up on Peer Preference: Parent-Child Interaction and Child Effortful Control as Sequential Mediators

    PubMed Central

    Shaw, Daniel S.; Shelleby, Elizabeth C.; Dishion, Thomas J.; Wilson, Melvin N.

    2018-01-01

    We examined the longitudinal effects of the Family Check-Up (FCU) intervention beginning in toddlerhood on children’s peer preference at school-age. Specifically, a sequential mediational model was proposed in which the FCU was hypothesized to promote peer preference (i.e., higher acceptance and lower rejection by peers) in middle childhood through its positive effects on parent-child interaction and child effortful control in early childhood. Participants were 731 low-income families (49 % female). Qualities of parent-child interaction were observed during structured activities at 2 to 5 years, child effortful control was assessed using behavioral tasks at 5 years, and peer acceptance and rejection were rated by teachers at 7.5 to 10.5 years. Results indicated that the FCU indirectly predicted peer preference by sequentially improving parent-child interaction and child effortful control. The findings are discussed with respect to implications for understanding mechanisms by which early parenting-focused programs may enhance child functioning across time and context. PMID:27558394

  14. The European FP7 ULTimateCO2 project: A comprehensive approach to study the long term fate of CO2 geological storage sites

    NASA Astrophysics Data System (ADS)

    Audigane, P.; Brown, S.; Dimier, A.; Pearce, J.; Frykman, P.; Maurand, N.; Le Gallo, Y.; Spiers, C. J.; Cremer, H.; Rutters, H.; Yalamas, T.

    2013-12-01

    The European FP7 ULTimateCO2 project aims at significantly advance our knowledge of specific processes that could influence the long-term fate of geologically stored CO2: i) trapping mechanisms, ii) fluid-rock interactions and effects on mechanical integrity of fractured caprock and faulted systems and iii) leakage due to mechanical and chemical damage in the well vicinity, iv) brine displacement and fluid mixing at regional scale. A realistic framework is ensured through collaboration with two demonstration sites in deep saline sandstone formations: the onshore former NER300 West Lorraine candidate in France (ArcelorMittal GeoLorraine) and the offshore EEPR Don Valley (former Hatfield) site in UK operated by National Grid. Static earth models have been generated at reservoir and basin scale to evaluate both trapping mechanisms and fluid displacement at short (injection) and long (post injection) time scales. Geochemical trapping and reservoir behaviour is addressed through experimental approaches using sandstone core materials in batch reactive mode with CO2 and impurities at reservoir pressure and temperature conditions and through geochemical simulations. Collection of data has been generated from natural and industrial (oil industry) analogues on the fluid flow and mechanical properties, structure, and mineralogy of faults and fractures that could affect the long-term storage capacity of underground CO2 storage sites. Three inter-related lines of laboratory experiments investigate the long-term evolution of the mechanical properties and sealing integrity of fractured and faulted caprocks using Opalinus clay of Mont Terri Gallery (Switzerland) (OPA), an analogue for caprock well investigated in the past for nuclear waste disposal purpose: - Characterization of elastic parameters in intact samples by measuring strain during an axial experiment, - A recording of hydraulic fracture flow properties by loading and shearing samples in order to create a 'realistic' fracture, followed by a gas injection in the fracture plan, - An assessment of temperature influences on carbonate and water content which affect carbonate bearing fault gouge using shear experiments at 20C and 120C on simulated fault gouges prepared by crushed OPA samples. To evaluate the interactions between CO2 (and formation fluids) and the well environment (formation, cement, casing) and to assess the consequences of these interactions on the transport properties of well materials, a 1:1 scale experiment has been set in the OPA to reproduce classical well objects (cemented annulus, casing and cement plug) perforating caprock formations (OPA). Innovative probabilistic modelling tools are also under development in order to build robust calibration methods for uncertainty management of the simulated long term scenarios.

  15. "Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model.

    PubMed

    Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Santa Cruz, Gustavo A; Trivillin, Verónica A; Schwint, Amanda E

    2011-04-01

    In the present study the therapeutic effect and potential toxicity of the novel "Sequential" boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential" BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential" BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ± 2% and 91 ± 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ± 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ± 12% and 60 ± 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential" BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue. © 2011 by Radiation Research Society

  16. Abusive Supervision by Academic Supervisors and Postgraduate Research Students' Creativity: The Mediating Role of Leader-Member Exchange and Intrinsic Motivation

    ERIC Educational Resources Information Center

    Meng, Yi; Tan, Jing; Li, Jing

    2017-01-01

    Drawing upon the componential theory of creativity, cognitive evaluation theory and social exchange theory, the study reported in this paper tested a mediating model based on the hypothesis that abusive supervision negatively influences creativity sequentially through leader-member exchange (LMX) and intrinsic motivation. The study employed…

  17. A Guide to Analyzing Message-Response Sequences and Group Interaction Patterns in Computer-Mediated Communication

    ERIC Educational Resources Information Center

    Jeong, Allan

    2005-01-01

    This paper proposes a set of methods and a framework for evaluating, modeling, and predicting group interactions in computer-mediated communication. The method of sequential analysis is described along with specific software tools and techniques to facilitate the analysis of message-response sequences. In addition, the Dialogic Theory and its…

  18. Maternal Mind-Mindedness and Children's School Readiness: A Longitudinal Study of Developmental Processes

    ERIC Educational Resources Information Center

    Bernier, Annie; McMahon, Catherine A.; Perrier, Rachel

    2017-01-01

    This study aimed to test a 5-wave sequential mediation model linking maternal mind-mindedness during infancy to children's school readiness in kindergarten through a serial mediation involving child language and effortful control in toddlerhood and the preschool years. Among a sample of 204 mother-child dyads, we assessed maternal mind-mindedness…

  19. Using Nazarov Electrocyclization to Stage Chemoselective [1,2]-Migrations: Stereoselective Synthesis of Functionalized Cyclopentenones

    PubMed Central

    Lebœuf, David; Huang, Jie; Gandon, Vincent

    2012-01-01

    Highly functionalized cyclopentenones are prepared stereospecifically based on a chemoselective copper(II)-mediated Nazarov/Wagner-Meerwein rearrangement sequence. After the initial 4π electrocyclization, this reaction involves two sequential [1,2]-migrations depending upon both migratory ability and steric bulk of the substituents at C1 and C5. This sequence can be achieved by using a catalytic quantity of copper(II) in combination with a weak Lewis acid. The mechanism of the reaction is also supported by DFT computations. PMID:21953873

  20. Symposium I: Nanoscale Magnetic Materials and Applications. Held in Boston, Massachusetts on November 25-30, 2007

    DTIC Science & Technology

    2008-06-01

    preparation of the exposed edge MTJ were performed. In- plane magnetization and cooling to 77 K further decreased the MMJ current to 1-1OpA level (1OOmV...temperature magnetic anneals due to dissimilar CoFeB/MgO interfaces. The effect is reduced by half for a bias of 1.88V, and the largest output voltage of...field induced interactions between the FM and AFM layers. Most of the studies dealt with in- plane angular dependence of magnetization hysteresis for FM

  1. The PL/OPA Multichannel Transmissometer Control and Data Acquisition System

    DTIC Science & Technology

    1990-12-12

    System Calibration and Data Reduction Voltages vi output from the transmissometer measuring beam attenuation over an 7 atmospheric path must be...supporting measurements of extinction and particle counts from visibility meters (0.89 pm) and Particle Measurement Systems aerosol distrometers respectively...The Multichannel Transmissometer is shown schematically in Figures 2.0-1 and 2.0-2. Measurements are made over the two-way path from transmitter

  2. Examination of Neisseria Gonorrhoeae Opacity Protein Expression During Experimental Murine Genital Tract Infection

    DTIC Science & Technology

    2005-01-01

    These alterations abolished Opa-dependent invasion. Also, cells deficient in proteoglycan synthesis were resistant to gonococcal invasion...volunteers. Gonococcal mutants deficient in production of pilin (40), RecA (40), or IgA1 protease (106) were not attenuated in this model. Interestingly...proliferative or high estrogen phase of the menstrual cycle. Endocervical cultures from these same patients taken during the luteal or high progesterone

  3. Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes

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

    Seo, MiRan; Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr

    Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the {alpha} subunit of Gq protein (G{alpha}q) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active G{alpha}q (G{alpha}qQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of G{alpha}q with shRNA in HaCaT human keratinocytes. G{alpha}q was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipasemore » C (PLC), protein kinase C{delta} (PKC{delta}), and matrix metaloprotease-2 (MMP-2). Moreover, G{alpha}qQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that G{alpha}q mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKC{delta} and MMP-2 in HaCaT cells.« less

  4. Development of the 1.6μm OPG/OPA system wavelength-controlled precisely for CO2 DIAL

    NASA Astrophysics Data System (ADS)

    Abo, M.; Shibata, Y.; Nagasawa, C.

    2010-12-01

    We developed an optical parametric oscillator (OPO) laser system for 1.6μm CO2 DIAL1). In order to improve the measurement accuracy of CO2 profiles, development of high power and wavelength stabilized laser system has been conducted. We report a new high-power 1.6μm laser transmitter based on a parametric master oscillator-power amplifier (MOPA) system pumped by a LD-pumped Q-switched Nd:YAG laser which has the injection seed laser locked to the iodine absorption line. The master oscillator is an optical parametric generator (OPG), based on an MgO-doped periodically poled LiTaO3 (PPMgLT) crystal. The OPOs require either active control of the cavity length or slight misalignment of the cavity. On the other hand, the OPGs do not require a cavity and instead rely on sufficient conversion efficiency to be obtained with a single pass through the crystal. The single-frequency oscillation of the OPG was achieved by injection seeding. The 1.6μm emission of the OPG is amplified by two-stage optical parametric amplifiers (OPAs). The each PPMgLT crystal was mounted on the copper holder, and the temperature control of the each holder was carried out within 0.01 K. The wavelength feedback system of the Nd:YAG seed laser is performed with the side locking of the iodine absorption spectrum (line No.1107) and the frequency stability is realized within 10 MHz rms. Stabilization of the 1.6μm DFB seed laser is estimated to within 4 MHz rms at the CO2 absorption line center and within 1.8 MHz rms at the CO2 absorption line slope using the wavelength control unit. We demonstrated single-longitudinal-mode emission with the OPG and two OPAs. The beam quality was TEM00 mode, the pulse energy was 12 mJ at 500 Hz repetition rate and the frequency stability was less than 10MHz rms. The unique performances of this optical parametric system make a relevant transmitter for CO2 DIAL. This work was financially supported by the System Development Program for Advanced Measurement and Analysis of the Japan Science and Technology Agency. Reference (1) D. Sakaisawa, C. Nagasawa, T. Nagai, M. Abo, Y. Shibata, H. Nagai, M. Nakazato, and T. Sakai, Development of a 1.6μm differential absorption lidar with a quasi-phase-matching optical parametric oscillator and photon-counting detector for the vertical CO2 profile, Applied Optics, Vol.48, No.4, pp.748-757, 2009.

  5. Advanced treatment of residual nitrogen from biologically treated coke effluent by a microalga-mediated process using volatile fatty acids (VFAs) under stepwise mixotrophic conditions.

    PubMed

    Ryu, Byung-Gon; Kim, Woong; Heo, Sung-Woon; Kim, Donghyun; Choi, Gang-Guk; Yang, Ji-Won

    2015-09-01

    This work describes the development of a microalga-mediated process for simultaneous removal of residual ammonium nitrogen (NH4(+)-N) and production of lipids from biologically treated coke effluent. Four species of green algae were tested using a sequential mixotrophic process. In the first phase-CO2-supplied mixotrophic condition-all microalgae assimilated NH4(+)-N with no evident inhibition. In second phase-volatile fatty acids (VFAs)-supplied mixotrophic condition-removal rates of NH4(+)-N and biomass significantly increased. Among the microalgae used, Arctic Chlorella sp. ArM0029B had the highest rate of NH4(+)-N removal (0.97 mg/L/h) and fatty acid production (24.9 mg/L/d) which were 3.6- and 2.1-fold higher than those observed under the CO2-supplied mixotrophic condition. Redundancy analysis (RDA) indicated that acetate and butyrate were decisive factors for increasing NH4(+)-N removal and fatty acid production. These results demonstrate that microalgae can be used in a sequential process for treatment of residual nitrogen after initial treatment of activated sludge. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Oil Pollution Act (OPA) and Federal Facilities

    EPA Pesticide Factsheets

    The Oil Pollution Prevention regulation sets forth requirements for prevention of, preparedness for, and response to oil discharges at specific non-transportation-related facilities, including federal facilities.

  7. Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir

    PubMed Central

    Montaner, Luis J.

    2017-01-01

    Abstract Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure. PMID:28520969

  8. Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India

    PubMed Central

    Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

    2014-01-01

    In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). PMID:25008901

  9. [Determination of fumonisins B1 and B2 in corn by high performance liquid chromatography with post-column derivatization method].

    PubMed

    Zhang, Xiaoxu; Xiao, Zhiyong; Zhang, Hongyan; Yang, Lili; Ma, Liyan

    2012-08-01

    A high performance liquid chromatography-fluorescence detection with post-column derivatization method was developed to detect fumonisin B1 (FB1) and fumonisin B2 (FB2) in corn. Several factors, such as the pH of derivatization buffer, concentration and flow rate of derivatization reagents, excitation wavelength, emission wavelength, which affected the detection of fumonisins were optimized. The separation was performed on a ZORBAX SB C18 column operated at 40 degrees C with the gradient elution by two mobile phases of 0.1 mol/L sodium dihydrogen phosphate solution (pH 3.3) and methanol at a flow rate of 0.8 mL/min. The derivatization was performed at ambient temperature. The o-phthalaldehyde (OPA) flow rate was 0.4 mL/min. The results showed that the optimum conditions were pH 10.5 of the derivatization reagent, OPA concentration at 2 g/L, and excitation wavelength of 335 nm, emission wavelength of 440 nm. The linear plots of FB1 and FB2 were obtained between 0.2 to 20 mg/L, with the correlation coefficients above 0.999 for both FB1 and FB2. The limits of detection of fumonisins B1 and B2 were 0.02 mg/kg. The mean recoveries at the three spiked levels of 0.1 - 4.0 mg/kg were 82.5% - 89.8%. This method is accurate, simple, rapid and suitable for the determination of fumonisins B1 and B2 in corn.

  10. Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

    PubMed

    Tunheim, G; Arnemo, M; Næss, L M; Fjeldheim, Å K; Nome, L; Bolstad, K; Aase, A; Mandiarote, A; González, H; González, D; García, L; Cardoso, D; Norheim, G; Rosenqvist, E

    2013-12-09

    Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Experimental realization of a feedback optical parametric amplifier with four-wave mixing

    NASA Astrophysics Data System (ADS)

    Pan, Xiaozhou; Chen, Hui; Wei, Tianxiang; Zhang, Jun; Marino, Alberto M.; Treps, Nicolas; Glasser, Ryan T.; Jing, Jietai

    2018-04-01

    Optical parametric amplifiers (OPAs) play a fundamental role in the generation of quantum correlation for quantum information processing and quantum metrology. In order to increase the communication fidelity of the quantum information protocol and the measurement precision of quantum metrology, it requires a high degree of quantum correlation. In this Rapid Communication we report a feedback optical parametric amplifier that employs a four-wave mixing (FWM) process as the underlying OPA and a beam splitter as the feedback controller. We first construct a theoretical model for this feedback-based FWM process and experimentally study the effect of the feedback control on the quantum properties of the system. Specifically, we find that the quantum correlation between the output fields can be enhanced by tuning the strength of the feedback.

  12. An Autoregulatory Pathway Establishes the Definitive Chromatin Conformation at the Pit-1 Locus

    PubMed Central

    Cooke, Nancy E.; Liebhaber, Stephen A.

    2015-01-01

    The transcription factor Pit-1 (POU1-F1) plays a dominant role in cell lineage expansion and differentiation in the anterior pituitary. Prior studies of the mouse Pit-1 (mPit-1) gene revealed that this master regulatory locus is activated at embryonic day 13.5 (E13.5) by an early enhancer (EE), whereas its subsequent expression throughout adult life is maintained by a more distal definitive enhancer (DE). Here, we demonstrate that the sequential actions of these two enhancers are linked to corresponding shifts in their proximities to the Pit-1 promoter. We further demonstrate that the looping of the definitive enhancer to the mPit-1 promoter is critically dependent on a self-sustaining autoregulatory mechanism mediated by the Pit-1 protein. These Pit-1-dependent actions are accompanied by localized recruitment of CBP and enrichment for H3K27 acetylation within the Pit-1 locus. These data support a model in which the sequential actions of two developmentally activated enhancers are linked to a corresponding shift in higher-order chromatin structures. This shift establishes an autoregulatory circuit that maintains durable expression of Pit-1 throughout adult life. PMID:25691665

  13. A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.

    PubMed

    Katz, Bradley J; Zhao, Yu; Warner, Judith E A; Tong, Zongzhong; Yang, Zhenglin; Zhang, Kang

    2006-10-15

    Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation Idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (LOD score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such as glaucoma and ischemic optic neuropathy. (c) 2006 Wiley-Liss, Inc.

  14. State of Washington, Aquatic Plant Management Program: Design Memorandum.

    DTIC Science & Technology

    1979-10-01

    3 days after appit- cation, fed ior 90 da- fo11-nIng haorst1ing equipment catIon. Swimming shouldt oe aplication . oring narventing opa- restricted...labor, maintenance, profit, capitalization of equipment costs, and mobilization -demobilization. 2/Local administrative costs are $2,000 for 100 acres...rental of two boats at a cost of $64/day each, mobilization - demobilization of equipment, and a capability of treating 100 acres/day. 2/The treatment boat

  15. Integrated on-chip derivatization and electrophoresis for the rapid analysis of biogenic amines.

    PubMed

    Beard, Nigel P; Edel, Joshua B; deMello, Andrew J

    2004-07-01

    We demonstrate the monolithic integration of a chemical reactor with a capillary electrophoresis device for the rapid and sensitive analysis of biogenic amines. Fluorescein isothiocyanate (FITC) is widely employed for the analysis of amino-group containing analytes. However, the slow reaction kinetics hinders the use of this dye for on-chip labeling applications. Other alternatives are available such as o-phthaldehyde (OPA), however, the inferior photophysical properties and the UV lambdamax present difficulties when using common excitation sources leading to a disparity in sensitivity. Consequently, we present for the first time the use of dichlorotriazine fluorescein (DTAF) as a superior in situ derivatizing agent for biogenic amines in microfluidic devices. The developed microdevice employs both hydrodynamic and electroosmotic flow, facilitating the creation of a polymeric microchip to perform both precolumn derivatization and electrophoretic analysis. The favorable photophysical properties of the DTAF and its fast reaction kinetics provide detection limits down to 1 nM and total analysis times (including on-chip mixing and reaction) of <60 s. The detection limits are two orders of magnitude lower than current limits obtained with both FITC and OPA. The optimized microdevice is also employed to probe biogenic amines in real samples.

  16. Determination of ammonium on an integrated microchip with LED-induced fluorescence detection.

    PubMed

    Xue, Shuhua; Uchiyama, Katsumi; Li, Hai-Fang

    2012-01-01

    A simply fabricated microfluidic device integrated with a fluorescence detection system has been developed for on-line determination of ammonium in aqueous samples. A 365-nm light-emitting diode (LED) as an excitation source and a minor band pass filter were mounted into a polydimethylsiloxane (PDMS)-based microchip for the purpose of miniaturization of the entire analytical system. The ammonium sample reacted with o-phthaldialdehyde (OPA) on-chip with sodium sulfite as reducing reagent to produce a fluorescent isoindole derivative, which can emit fluorescence signal at about 425 nm when excited at 365 nm. Effects of pH, flow rate of solutions, concentrations of OPA-reagent, phosphate and sulfite salt were investigated. The calibration curve of ammonium in the range of 0.018-1.8 microg/mL showed a good linear relationship with R2 = 0.9985, and the detection limit was (S/N = 3) 3.6 x 10(-4) microg/mL. The relative standard deviation was 2.8% (n = 11) by calculating at 0.18 microg/mL ammonium for repeated detection. The system was applied to determine the ammonium concentration in rain and river waters, even extent to other analytes fluorescence detection by the presented device.

  17. ATP binding cassette G1-dependent cholesterol efflux during inflammation.

    PubMed

    de Beer, Maria C; Ji, Ailing; Jahangiri, Anisa; Vaughan, Ashley M; de Beer, Frederick C; van der Westhuyzen, Deneys R; Webb, Nancy R

    2011-02-01

    ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent efflux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A(2) (sPLA(2)-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.

  18. Relationships among race, education, criminal thinking, and recidivism: moderator and mediator effects.

    PubMed

    Walters, Glenn D

    2014-02-01

    Moderator and mediator relationships linking variables from three different theoretical traditions-race (subcultural theory), education (life-course theory), and criminal thinking (social learning theory)-and recidivism were examined in 1,101 released male federal prison inmates. Preliminary regression analyses indicated that racial status (White, Black, Hispanic) moderated the relationship between criminal thinking, as measured by the General Criminal Thinking (GCT) score of the Psychological Inventory of Criminal Thinking Styles (PICTS), and recidivism. Further analysis, however, revealed that it was not racial status, per se, that moderated the relationship between the PICTS and recidivism, but educational attainment. Whereas the PICTS was largely effective in predicting recidivism in inmates with 12 or more years of education, it was largely ineffective in predicting recidivism in inmates with fewer than 12 years of education. When education and the GCT score were compared as possible mediators of the race-recidivism relationship only the GCT successfully mediated this relationship. Sensitivity testing showed that the GCT mediating effect was moderately robust to violations of the sequential ignorability assumption on which causal mediation analysis rests. Moderator and mediator analyses are potentially important avenues through which theoretical constructs can be integrated and assessment strategies devised.

  19. The Temporal Sequence of Social Anxiety and Depressive Symptoms following Interpersonal Stressors during Adolescence

    PubMed Central

    Hamilton, Jessica L.; Potter, Carrie M.; Olino, Thomas M.; Abramson, Lyn Y.; Heimberg, Richard G.; Alloy, Lauren B.

    2015-01-01

    Social anxiety and depressive symptoms dramatically increase and frequently co-occur during adolescence. Although research indicates that general interpersonal stressors, peer victimization, and familial emotional maltreatment predict symptoms of social anxiety and depression, it remains unclear how these stressors contribute to the sequential development of these internalizing symptoms. Thus, the present study examined the sequential development of social anxiety and depressive symptoms following the occurrence of interpersonal stressors, peer victimization, and familial emotional maltreatment. Participants included 410 early adolescents (53% female; 51% African American; Mean age =12.84 years) who completed measures of social anxiety and depressive symptoms at three time points (Times 1–3), as well as measures of general interpersonal stressors, peer victimization, and emotional maltreatment at Time 2. Path analyses revealed that interpersonal stressors, peer victimization, and emotional maltreatment predicted both depressive and social anxiety symptoms concurrently. However, depressive symptoms significantly mediated the pathway from interpersonal stressors, peer victimization, and familial emotional maltreatment to subsequent levels of social anxiety symptoms. In contrast, social anxiety did not mediate the relationship between these stressors and subsequent depressive symptoms. There was no evidence of sex or racial differences in these mediational pathways. Findings suggest that interpersonal stressors, including the particularly detrimental stressors of peer victimization and familial emotional maltreatment, may predict both depressive and social anxiety symptoms; however, adolescents who have more immediate depressogenic reactions may be at greater risk for later development of symptoms of social anxiety. PMID:26142495

  20. The relationship between counselors' technical skills, clients' in-session verbal responses, and outcome in smoking cessation treatment.

    PubMed

    Lindqvist, Helena; Forsberg, Lars; Enebrink, Pia; Andersson, Gerhard; Rosendahl, Ingvar

    2017-06-01

    The technical component of Motivational Interviewing (MI) posits that client language mediates the relationship between counselor techniques and subsequent client behavioral outcomes. The purpose of this study was to examine this hypothesized technical component of MI in smoking cessation treatment in more depth. Secondary analysis of 106 first treatment sessions, derived from the Swedish National Tobacco Quitline, and previously rated using the Motivational Interviewing Sequential Code for Observing Process Exchanges (MI-SCOPE) Coder's Manual and the Motivational Interviewing Treatment Integrity code (MITI) Manual, version 3.1. The outcome measure was self-reported 6-month continuous abstinence at 12-month follow-up. Sequential analyses indicated that clients were significantly more likely than expected by chance to argue for change (change talk) following MI-consistent behaviors and questions and reflections favoring change. Conversely, clients were more likely to argue against change (sustain talk) following questions and reflections favoring status-quo. Parallel mediation analysis revealed that a counselor technique (reflections of client sustain talk) had an indirect effect on smoking outcome at follow-up through client language mediators. The study makes a significant contribution to our understanding of how MI works in smoking cessation treatment and adds further empirical support for the hypothesized technical component in MI. The results emphasize the importance of counselors avoiding unintentional reinforcement of sustain talk and underline the need for a greater emphasis on the direction of questions and reflections in MI trainings and fidelity measures. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The role of action control and action planning on fruit and vegetable consumption.

    PubMed

    Zhou, Guangyu; Gan, Yiqun; Miao, Miao; Hamilton, Kyra; Knoll, Nina; Schwarzer, Ralf

    2015-08-01

    Globally, fruit and vegetable intake is lower than recommended despite being an important component to a healthy diet. Adopting or maintaining a sufficient amount of fruit and vegetables in one's diet may require not only motivation but also self-regulatory processes. Action control and action planning are two key volitional determinants that have been identified in the literature; however, it is not fully understood how these two factors operate between intention and behavior. Thus, the aim of the current study was to explore the roles of action control and action planning as mediators between intentions and dietary behavior. A longitudinal study with three points in time was conducted. Participants (N = 286) were undergraduate students and invited to participate in a health behavior survey. At baseline (Time 1), measures of intention and fruit and vegetable intake were assessed. Two weeks later (Time 2), action control and action planning were assessed as putative sequential mediators. At Time 3 (two weeks after Time 2), fruit and vegetable consumption was measured as the outcome. The results revealed action control and action planning to sequentially mediate between intention and subsequent fruit and vegetable intake, controlling for baseline behavior. Both self-regulatory constructs, action control and action planning, make a difference when moving from motivation to action. Our preliminary evidence, therefore, suggests that planning may be more proximal to fruit and vegetable intake than action control. Further research, however, needs to be undertaken to substantiate this conclusion. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The Temporal Sequence of Social Anxiety and Depressive Symptoms Following Interpersonal Stressors During Adolescence.

    PubMed

    Hamilton, Jessica L; Potter, Carrie M; Olino, Thomas M; Abramson, Lyn Y; Heimberg, Richard G; Alloy, Lauren B

    2016-04-01

    Social anxiety and depressive symptoms dramatically increase and frequently co-occur during adolescence. Although research indicates that general interpersonal stressors, peer victimization, and familial emotional maltreatment predict symptoms of social anxiety and depression, it remains unclear how these stressors contribute to the sequential development of these internalizing symptoms. Thus, the present study examined the sequential development of social anxiety and depressive symptoms following the occurrence of interpersonal stressors, peer victimization, and familial emotional maltreatment. Participants included 410 early adolescents (53% female; 51% African American; Mean age =12.84 years) who completed measures of social anxiety and depressive symptoms at three time points (Times 1-3), as well as measures of general interpersonal stressors, peer victimization, and emotional maltreatment at Time 2. Path analyses revealed that interpersonal stressors, peer victimization, and emotional maltreatment predicted both depressive and social anxiety symptoms concurrently. However, depressive symptoms significantly mediated the pathway from interpersonal stressors, peer victimization, and familial emotional maltreatment to subsequent levels of social anxiety symptoms. In contrast, social anxiety did not mediate the relationship between these stressors and subsequent depressive symptoms. There was no evidence of sex or racial differences in these mediational pathways. Findings suggest that interpersonal stressors, including the particularly detrimental stressors of peer victimization and familial emotional maltreatment, may predict both depressive and social anxiety symptoms; however, adolescents who have more immediate depressogenic reactions may be at greater risk for later development of symptoms of social anxiety.

  3. Coordination of two sequential ester-transfer reactions: exogenous guanosine binding promotes the subsequent ωG binding to a group I intron

    PubMed Central

    Bao, Penghui; Wu, Qi-Jia; Yin, Ping; Jiang, Yanfei; Wang, Xu; Xie, Mao-Hua; Sun, Tao; Huang, Lin; Mo, Ding-Ding; Zhang, Yi

    2008-01-01

    Self-splicing of group I introns is accomplished by two sequential ester-transfer reactions mediated by sequential binding of two different guanosine ligands, but it is yet unclear how the binding is coordinated at a single G-binding site. Using a three-piece trans-splicing system derived from the Candida intron, we studied the effect of the prior GTP binding on the later ωG binding by assaying the ribozyme activity in the second reaction. We showed that adding GTP simultaneously with and prior to the esterified ωG in a substrate strongly accelerated the second reaction, suggesting that the early binding of GTP facilitates the subsequent binding of ωG. GTP-mediated facilitation requires C2 amino and C6 carbonyl groups on the Watson–Crick edge of the base but not the phosphate or sugar groups, suggesting that the base triple interactions between GTP and the binding site are important for the subsequent ωG binding. Strikingly, GTP binding loosens a few local structures of the ribozyme including that adjacent to the base triple, providing structural basis for a rapid exchange of ωG for bound GTP. PMID:18978026

  4. 15 CFR 990.11 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Introduction § 990.11 Scope. The Oil Pollution Act of 1990 (OPA), 33 U.S.C. 2701 et seq., provides...

  5. Anticipating conflict facilitates controlled stimulus-response selection

    PubMed Central

    Correa, Ángel; Rao, Anling; Nobre, Anna C.

    2014-01-01

    Cognitive control can be triggered in reaction to previous conflict, as suggested by the finding of sequential effects in conflict tasks. Can control also be triggered proactively by presenting cues predicting conflict (‘proactive control’)? We exploited the high temporal resolution of event-related potentials (ERPs) and controlled for sequential effects to ask whether proactive control based on anticipating conflict modulates neural activity related to cognitive control, as may be predicted from the conflict-monitoring model. ERPs associated with conflict detection (N2) were measured during a cued flanker task. Symbolic cues were either informative or neutral with respect to whether the target involved conflicting or congruent responses. Sequential effects were controlled by analysing the congruency of the previous trial. The results showed that cuing conflict facilitated conflict resolution and reduced the N2 latency. Other potentials (frontal N1 and P3) were also modulated by cuing conflict. Cuing effects were most evident after congruent than after incongruent trials. This interaction between cuing and sequential effects suggests neural overlap between the control networks triggered by proactive and reactive signals. This finding clarifies why previous neuroimaging studies, in which reactive sequential effects were not controlled, have rarely found anticipatory effects upon conflict-related activity. Finally, the high temporal resolution of ERPs was critical to reveal a temporal modulation of conflict detection by proactive control. This novel finding suggests that anticipating conflict speeds up conflict detection and resolution. Recent research suggests that this anticipatory mechanism may be mediated by pre-activation of the ACC during the preparatory interval. PMID:18823248

  6. Three-year-olds obey the sample size principle of induction: the influence of evidence presentation and sample size disparity on young children's generalizations.

    PubMed

    Lawson, Chris A

    2014-07-01

    Three experiments with 81 3-year-olds (M=3.62years) examined the conditions that enable young children to use the sample size principle (SSP) of induction-the inductive rule that facilitates generalizations from large rather than small samples of evidence. In Experiment 1, children exhibited the SSP when exemplars were presented sequentially but not when exemplars were presented simultaneously. Results from Experiment 3 suggest that the advantage of sequential presentation is not due to the additional time to process the available input from the two samples but instead may be linked to better memory for specific individuals in the large sample. In addition, findings from Experiments 1 and 2 suggest that adherence to the SSP is mediated by the disparity between presented samples. Overall, these results reveal that the SSP appears early in development and is guided by basic cognitive processes triggered during the acquisition of input. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

    PubMed

    Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

    2015-11-15

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

  8. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function

    PubMed Central

    Rajendran, Pradeep S.; Nier, Heath A.; KenKnight, Bruce H.; Armour, J. Andrew

    2015-01-01

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

  9. Guidance: Use of Contract Inspectors for EPA's Federal Facility Compliance Inspections/Evaluations

    EPA Pesticide Factsheets

    This guidance clarifies that properly trained authorized and federally credentialed EPA contract inspectors can perform compliance inspections at federal facilities under the CWA, RCRA, TSCA, OPA and the SDWA.

  10. [Genetic variability and differentiation of three Russian populations of yellow potato cyst nematode Globodera rostochiensis as revealed by nuclear markers].

    PubMed

    Khrisanfova, G G; Kharchevnikov, D A; Popov, I O; Zinov'eva, S V; Semenova, S K

    2008-05-01

    Genetic variability of yellow potato cyst nematode G. rostochiensis from three Russian populations (Karelia, Vladimir oblast, and Moscow oblast) was investigated using two types of nuclear markers. Using RAPD markers identified with the help of six random primers (P-29, OPA-10, OPT-14, OPA-11, OPB-11, and OPH-20), it was possible to distinguish Karelian population from the group consisting of the populations from two adjacent regions (Moscow oblast and Vladimir oblast). Based on the combined matrix, containing 294 RAPD fragments, dendrogram of genetic differences was constructed, and the indices of genetic divergence and partition (P, H, and G(st)), as well as the gene flow indices N(m) between the nematode samples examined, were calculated. The dendrogram structure, genetic diversity indices, and variations of genetic distances between single individuals in each population from Karelia and Central Russia pointed to genetic isolation and higher genetic diversity of the nematodes from Karelia. Based on polymorphism of rDNA first intergenic spacer ITS1, attribution of all populations examined to the species G. rostochiensis was proved. Small variations of the ITS1 sequence in different geographic populations of nematodes from different regions of the species world range did not allow isolation of separate groups within the species. Possible factors (including interregional transportations of seed potato) affecting nematode population structure in Russia are discussed.

  11. Phase-matching properties of BaGa4Se7 for SHG and SFG in the 0.901-10.5910  μm range.

    PubMed

    Kato, Kiyoshi; Miyata, Kentaro; Petrov, Valentin

    2017-04-10

    We report new experimental results on the phase-matching properties of a BaGa4Se7 crystal for harmonic generation of a Nd:YAG laser-pumped AgGaS2 optical parametric oscillator (OPO) and a CO2 laser in the 0.901-10.5910 μm range. In addition, we present new Sellmeier equations that provide a good reproduction of the present experimental results as well as the published data points for a Nd:YAG laser-pumped OPO and an optical parametric amplifier (OPA) in the 3.10-15.22 μm range and a Ho:YAG laser-pumped OPA in the 3.49-5.18 μm range.

  12. Precision resection of lung cancer in a sheep model using ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Beck, Rainer J.; Mohanan, Syam Mohan P. C.; Góra, Wojciech S.; Cousens, Chris; Finlayson, Jeanie; Dagleish, Mark P.; Griffiths, David J.; Shephard, Jonathan D.

    2017-02-01

    Recent developments and progress in the delivery of high average power ultrafast laser pulses enable a range of novel minimally invasive surgical procedures. Lung cancer is the leading cause of cancer deaths worldwide and here the resection of lung tumours by means of picosecond laser pulses is presented. This represents a potential alternative to mitigate limitations of existing surgical treatments in terms of precision and collateral thermal damage to the healthy tissue. Robust process parameters for the laser resection are demonstrated using ovine pulmonary adenocarcinoma (OPA). OPA is a naturally occurring lung cancer of sheep caused by retrovirus infection that has several features in common with some forms of human pulmonary adenocarcinoma, including a similar histological appearance, which makes it ideally suited for this study. The picosecond laser was operated at a wavelength of 515 nm to resect square cavities from fresh ex-vivo OPA samples using a range of scanning strategies. Process parameters are presented for efficient ablation of the tumour with clear margins and only minimal collateral damage to the surrounding tissue. The resection depth can be controlled precisely by means of the pulse energy. By adjusting the overlap between successive laser pulses, deliberate heat transfer to the tissue and thermal damage can be achieved. This can be beneficial for on demand haemostasis and laser coagulation. Overall, the application of ultrafast lasers for the resection of lung tumours has potential to enable significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional techniques.

  13. A Low Cost Rokkaku Kite Setup for Aerial Photogrammetric System

    NASA Astrophysics Data System (ADS)

    Khan, A. F.; Khurshid, K.; Saleh, N.; Yousuf, A. A.

    2015-03-01

    Orthogonally Projected Area (OPA) of a geographical feature has primarily been studied utilizing rather time consuming field based sampling techniques. Remote sensing on the contrary provides the ability to acquire large scale data at a snapshot of time and lets the OPA to be calculated conveniently and with reasonable accuracy. Unfortunately satellite based remote sensing provides data at high cost and limited spatial resolution for scientific studies focused at small areas such as micro lakes micro ecosystems, etc. More importantly, recent satellite data may not be readily available for a particular location. This paper describes a low cost photogrammetric system to measure the OPA of a small scale geographic feature such as a plot of land, micro lake or an archaeological site, etc. Fitted with a consumer grade digital imaging system, a Rokkaku kite aerial platform with stable flight characteristics is designed and fabricated for image acquisition. The data processing procedure involves automatic Ground Control Point (GCP) detection, intelligent target area shape determination with minimal human input. A Graphical User Interface (GUI) is built from scratch in MATLAB to allow the user to conveniently process the acquired data, archive and retrieve the results. Extensive on-field experimentation consists of multiple geographic features including flat land surfaces, buildings, undulating rural areas, and an irregular shaped micro lake, etc. Our results show that the proposed system is not only low cost, but provides a framework that is easy and fast to setup while maintaining the required constraints on the accuracy.

  14. Titanium(IV) isopropoxide mediated synthesis of pyrimidin-4-ones.

    PubMed

    Ramanjulu, Joshi M; Demartino, Michael P; Lan, Yunfeng; Marquis, Robert

    2010-05-21

    A novel, one-step method for the synthesis of tri- and tetrasubstituted pyrimidin-4-ones is reported. This method involves a titanium(IV)-mediated cyclization involving two sequential condensations of primary and beta-ketoamides. The reaction is operationally facile, readily scalable, and offers rapid entry into differentially substituted pyrimidin-4-one scaffolds. The high functional group compatibility allows for substantial diversification in the products generated from this transformation.

  15. Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir.

    PubMed

    Riley, James L; Montaner, Luis J

    2017-03-15

    Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  16. Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein.

    PubMed

    Martinez, Jimena Hebe; Alaimo, Agustina; Gorojod, Roxana Mayra; Porte Alcon, Soledad; Fuentes, Federico; Coluccio Leskow, Federico; Kotler, Mónica Lidia

    2018-04-01

    Parkinson's disease is a neurodegenerative movement disorder caused by the loss of dopaminergic neurons from substantia nigra. It is characterized by the accumulation of aggregated α-synuclein as the major component of the Lewy bodies. Additional common features of this disease are the mitochondrial dysfunction and the activation/inhibition of autophagy both events associated to the intracellular accumulation of α-synuclein. The mechanism by which these events contribute to neural degeneration remains unknown. In the present work we investigated the effect of α-synuclein on mitochondrial dynamics and autophagy/mitophagy in SH-SY5Y cells, an in vitro model of Parkinson disease. We demonstrated that overexpression of wild type α-synuclein causes moderated toxicity, ROS generation and mitochondrial dysfunction. In addition, α-synuclein induces the mitochondrial fragmentation on a Drp-1-dependent fashion. Overexpression of the fusion protein Opa-1 prevented both mitochondrial fragmentation and cytotoxicity. On the other hand, cells expressing α-synuclein showed activated autophagy and particularly mitophagy. Employing a genetic strategy we demonstrated that autophagy is triggered in order to protect cells from α-synuclein-induced cell death. Our results clarify the role of Opa-1 and Drp-1 in mitochondrial dynamics and cell survival, a controversial α-synuclein research issue. The findings presented point to the relevance of mitochondrial homeostasis and autophagy in the pathogenesis of PD. Better understanding of the molecular interaction between these processes could give rise to novel therapeutic methods for PD prevention and amelioration. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Laccase pretreatment for agrofood wastes valorization.

    PubMed

    Giacobbe, Simona; Pezzella, Cinzia; Lettera, Vincenzo; Sannia, Giovanni; Piscitelli, Alessandra

    2018-06-01

    Apple pomace, potato peels, and coffee silverskin are attractive agrofood wastes for the production of biofuels and chemicals, due to their abundance and carbohydrate content. As lignocellulosic biomasses, their conversion is challenged by the presence of lignin that prevents hydrolysis of polysaccharides, hence demanding a pretreatment step. In this work, the effectiveness of Pleurotus ostreatus laccases (with and without mediator) to remove lignin, improving the subsequent saccharification, was assessed. Optimized conditions for sequential protocol were set up for all agrofood wastes reaching delignification and detoxification yields correlated with high saccharification. Especially noteworthy were results for apple pomace and coffee silverskin for which 83% of and 73% saccharification yields were observed, by using laccase and laccase mediator system, respectively. The herein developed sequential protocol, saving soluble sugars and reducing the amount of wastewater, can improve the overall process for obtaining chemicals or fuels from agrofood wastes. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. Where are we coming from versus who we will become: the effect of priming different contents of European identity on cooperation.

    PubMed

    La Barbera, Francesco; Ferrara, Pia Cariota; Boza, Mihaela

    2014-12-01

    In two experiments, we investigated how priming European identity as common project versus common heritage affects participants' cooperation in a social dilemma; an additional aim was to explore the mediators involved in the process. In the first experiment, 82 students played a public good dilemma with a European bogus partner and then completed self-report measures of identification with the European Union (EU), group-based trust and collective interest. Results showed that priming a common project-based but not a common heritage-based European social identity fostered cooperative behaviour; this effect was mediated by two sequential mediators: the common project prime increased participants' strength of identification with EU (mediator 1) which, in turn, positively affected group-based trust (mediator 2), fostering greater cooperation. Experiment 2 was conducted with a similar procedure on a sample of 124 students, using a different measure of trust and changing the order of mediators. Results supported those of previous experiment: Priming a project-based EU identity content (compared to heritage-based one) had significant direct and indirect effects on cooperation. © 2014 International Union of Psychological Science.

  19. A Novel System for Simultaneous or Sequential Integration of Multiple Gene-Loading Vectors into a Defined Site of a Human Artificial Chromosome

    PubMed Central

    Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

    2014-01-01

    Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming. PMID:25303219

  20. A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

    PubMed

    Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

    2014-01-01

    Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

  1. Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development.

    PubMed

    Deng, Qiannan; Guo, Ting; Zhou, Xiu; Xi, Yongmei; Yang, Xiaohang; Ge, Wanzhong

    2016-08-01

    Cell proliferation and tissue growth depend on the coordinated regulation of multiple signaling molecules and pathways during animal development. Previous studies have linked mitochondrial function and the Hippo signaling pathway in growth control. However, the underlying molecular mechanisms are not fully understood. Here we identify a Drosophila mitochondrial inner membrane protein ChChd3 as a novel regulator for tissue growth. Loss of ChChd3 leads to tissue undergrowth and cell proliferation defects. ChChd3 is required for mitochondrial fusion and removal of ChChd3 increases mitochondrial fragmentation. ChChd3 is another mitochondrial target of the Hippo pathway, although it is only partially required for Hippo pathway-mediated overgrowth. Interestingly, lack of ChChd3 leads to inactivation of Hippo activity under normal development, which is also dependent on the transcriptional coactivator Yorkie (Yki). Furthermore, loss of ChChd3 induces oxidative stress and activates the JNK pathway. In addition, depletion of other mitochondrial fusion components, Opa1 or Marf, inactivates the Hippo pathway as well. Taken together, we propose that there is a cross-talk between mitochondrial fusion and the Hippo pathway, which is essential in controlling cell proliferation and tissue homeostasis in Drosophila. Copyright © 2016 by the Genetics Society of America.

  2. Interferon-γ converts human microvascular pericytes into negative regulators of alloimmunity through induction of indoleamine 2,3-dioxygenase 1

    PubMed Central

    Liu, Rebecca; Manes, Thomas D.; Qin, Lingfeng; Tietjen, Gregory T.; Broecker, Verena; Fang, Caodi; Xie, Catherine; Chen, Ping-Min; Kirkiles-Smith, Nancy C.; Jane-Wit, Dan; Pober, Jordan S.

    2018-01-01

    Early acute rejection of human allografts is mediated by circulating alloreactive host effector memory T cells (TEM). TEM infiltration typically occurs across graft postcapillary venules and involves sequential interactions with graft-derived endothelial cells (ECs) and pericytes (PCs). While the role of ECs in allograft rejection has been extensively studied, contributions of PCs to this process are largely unknown. This study aimed to characterize the effects and mechanisms of interactions between human PCs and allogeneic TEM. We report that unstimulated PCs, like ECs, can directly present alloantigen to TEM, but while IFN-γ–activated ECs (γ-ECs) show increased ability to stimulate alloreactive T cells, IFN-γ–activated PCs (γ-PCs) instead suppress TEM proliferation but not cytokine production or signaling. RNA sequencing analysis of PCs, γ-PCs, ECs, and γ-ECs reveal induction of indoleamine 2,3-dioxygenase 1 (IDO1) in γ-PCs to significantly higher levels than in γ-ECs that correlates with tryptophan depletion in vitro. Consistently, shRNA knockdown of IDO1 markedly reduces γ-PC–mediated immunoregulatory effects. Furthermore, human PCs express IDO1 in a skin allograft rejection humanized mouse model and in human renal allografts with acute T cell–mediated rejection. We conclude that immunosuppressive properties of human PCs are not intrinsic but instead result from IFN-γ–induced IDO1-mediated tryptophan depletion. PMID:29515027

  3. Laminar shear stress promotes mitochondrial homeostasis in endothelial cells.

    PubMed

    Wu, Li-Hong; Chang, Hao-Chun; Ting, Pei-Ching; Wang, Danny L

    2018-06-01

    Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm 2 ) generated by a parallel-plate flow chamber system. ECs subjected to LSS demonstrated an increment of mitochondria in tubular form coupled with the increase of fusion proteins (Mfn2, OPA1) and the decrease of fission protein (Fis1). An increase of both long- and short- OPA1 along with a higher protease YME1L level were observed. LSS triggered a rapid phosphorylation on S637 but a decrease on S616 of fission-controlled protein Drp1. Consistently, Drp1 translocation to mitochondria was decreased in sheared ECs, suggesting that LSS promotes mitochondrial fusion. Enhanced mitochondrial biogenesis in sheared ECs was shown by the increase of mitochondrial mass and its regulatory proeins (PGC1α, TFAM, Nrf1). LSS enhances the expression of mitochondrial antioxidant enzymes and improves mitochondrial functions indicated by the increase of mitochondrial membrane potential (ΔΨm) and ATP generation. TNFα treatment decreased mitochondrial tubular network and its functions in ECs. LSS mitigated TNFα-induced mitochondrial impairments in ECs. Our results clearly indicate that LSS promotes mitochondrial homeostasis and attenuates inflammation-induced mitochondrial impairments in ECs. Our results provide novel insights into the manner of mitochondrial dynamics and functions modulated by LSS that contribute to endothelial integrity. © 2017 Wiley Periodicals, Inc.

  4. A toddler PCV booster dose following 3 infancy priming doses increases circulating serotype-specific IGG levels but does not increase protection against carriage.

    PubMed

    Dagan, Ron; Ben-Shimol, Shalom; Simell, Birgit; Greenberg, David; Porat, Nurith; Käyhty, Helena; Givon-Lavi, Noga

    2018-05-11

    We compared PCV7 serological response and protection against carriage in infants receiving 3 doses (2, 4, 6 months; 3+0 schedule) to those receiving a booster (12 months; 3+1). A prospective, randomized controlled study, conducted between 2005 and 2008, before PCVs were implemented in Israel. Healthy infants were randomized 1:1:1 to receive 3+1, 3+0 and 0+2 (control group; 12, 18 months doses). Nasopharyngeal/oropharyngeal swabs were obtained at all visits. Serum serotype-specific IgG concentrations and opsonic activities (OPA) were measured at 2, 7, 13 and 19 months. This study was registered with Current Controlled Trials, Ltd. ISRCTN28445844. Overall, 544 infants were enrolled: 3+1 (n = 178), 3+0 (n = 178) and 0+2 (n = 188). Post-priming (7 months), antibody concentrations were similar in both groups, except for serotype 18C (higher in 3+0). Post-booster (13, 19 months), ELISA and OPA levels were significantly higher in 3+1 than in 3+0 group. Nasopharyngeal/oropharyngeal cultures were positive for Streptococcus pneumoniae in 2673 (54.3%) visits. Acquisition rates (vaccine and non-vaccine serotypes) were similar for 3+1 and 3+0 groups at 7-30 months and for 0+2 group at 19-30 months. PCV7 booster after 3 priming doses increased substantially IgG concentrations but did not further reduced vaccine-serotype nasopharyngeal acquisition, suggesting that protection from pneumococcal carriage does not depend primarily on serum IgG. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Protect Yourself Against HPV | NIH MedlinePlus the Magazine

    MedlinePlus

    ... gov/opa/reproductive-health/stis/hpv/ Human Papillomavirus Block this cervical-cancer causing virus More than half ... against all these forms of cancer. Gardasil also blocks two HPV strains that cause 90 percent of ...

  6. Oil Pollution Research and Technology Plan

    DOT National Transportation Integrated Search

    1997-04-01

    Title VII of the Oil Pollution Act of 1990 (OPA 90) established the thirteen member Interagency Coordinating Committee on Oil Pollution Research (Committee). The Committee is charged with coordinating a comprehensive program of research, technology d...

  7. DNA-HMGB1 interaction: The nuclear aggregates of polyamine mediation.

    PubMed

    Iacomino, Giuseppe; Picariello, Gianluca; Sbrana, Francesca; Raiteri, Roberto; D'Agostino, Luciano

    2016-10-01

    Nuclear aggregates of polyamines (NAPs) are supramolecular compounds generated by the self-assembly of protonated nuclear polyamines (spermine, spermidine and putrescine) and phosphate ions. In the presence of genomic DNA, the hierarchical process of self-structuring ultimately produces nanotube-like polymers that envelop the double helix. Because of their modular nature and their aggregation-disaggregation dynamics, NAPs confer plasticity and flexibility to DNA. Through the disposition of charges, NAPs also enable a bidirectional stream of information between the genome and interacting moieties. High mobility group (HMG) B1 is a non-histone chromosomal protein that binds to DNA and that influences multiple nuclear processes. Because genomic DNA binds to either NAPs or HMGB1 protein, we explored the ability of in vitro self-assembled NAPs (ivNAPs) to mediate the DNA-HMGB1 interaction. To this end, we structured DNA-NAPs-HMGB1 and DNA-HMGB1-NAPs ternary complexes in vitro through opportune sequential incubations. Mobility shift electrophoresis and atomic force microscopy showed that the DNA-ivNAPs-HGMB1 complex had conformational assets supposedly more suitable those of the DNA-HGMB1-ivNAPs to comply with the physiological and functional requirements of DNA. Our findings indicated that ivNAPs act as mediators of the DNA-HMGB1 interaction. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Aclacinomycin A Sensitizes K562 Chronic Myeloid Leukemia Cells to Imatinib through p38MAPK-Mediated Erythroid Differentiation

    PubMed Central

    Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

    2013-01-01

    Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches. PMID:23613979

  9. Aclacinomycin A sensitizes K562 chronic myeloid leukemia cells to imatinib through p38MAPK-mediated erythroid differentiation.

    PubMed

    Lee, Yueh-Lun; Chen, Chih-Wei; Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

    2013-01-01

    Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches.

  10. Cloning and characterization of 2S albumin, Car i 1, a major allergen in pecan.

    PubMed

    Sharma, Girdhari M; Irsigler, Andre; Dhanarajan, Pushparani; Ayuso, Rosalia; Bardina, Luda; Sampson, Hugh A; Roux, Kenneth H; Sathe, Shridhar K

    2011-04-27

    Although pecans are associated with IgE-mediated food allergies, the allergens responsible remain to be identified and characterized. The 2S albumin gene was amplified from the pecan cDNA library. Dot-blots were used to screen the recombinant protein with pecan allergic patients' serum. The affinity purified native protein was analyzed by Edman sequencing and mass spectrometry/mass spectrometry (MS/MS) analysis. Cross-reactivity with walnut was determined by inhibition enzyme-linked immunosorbent assay (ELISA). Sequential epitopes were determined by probing the overlapping peptides with three different patients' serum pool. The 3-dimensional homology model was generated, and the locations of the pecan epitopes were compared with those of known sequential epitopes on other allergenic tree nut homologues. Of 28 patients tested by dot-blot, 22 (79%) bound to 2S albumin, designated as Car i 1. Edman sequencing and the MS/MS sequencing of native 2S albumin confirmed the identity of recombinant (r) Car i 1. Both pecan and walnut protein extracts inhibited the IgE-binding to rCar i 1. Sequential epitope mapping indicated weak, moderate, and strong reactivity against 12, 7, and 5 peptides, respectively. Of the 11 peptides recognized by all serum pools, 5 peptides were strongly reactive and located in 3 discrete regions of the Car i 1 (amino acids 43-57, 67-78, and 106-120). Three-dimensional modeling revealed IgE-reactive epitopes to be solvent accessible and share significant homology with other tree nuts providing a possible basis for previously observed cross-reactivity.

  11. Randomized, open-label study of the impact of age on booster responses to the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in children in India.

    PubMed

    Lalwani, Sanjay; Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

    2014-09-01

    In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells.

    PubMed

    Ohno, Tasuku; Yamamoto, Genta; Hayashi, Jun-Ichiro; Nishida, Eisaku; Goto, Hisashi; Sasaki, Yasuyuki; Kikuchi, Takeshi; Fukuda, Mitsuo; Hasegawa, Yoshiaki; Mogi, Makio; Mitani, Akio

    2017-01-01

    Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by inducing inflammation and angiogenesis. It is produced in infiltrating immune cells or resident cells, such as adipocytes, vascular endothelial cells, and tumor cells. We hypothesized that ANGPTL2 might play an important role as a unique mediator in both systemic and periodontal disease. We demonstrated an increased ANGPTL2 concentration in gingival crevicular fluid from chronic periodontitis patients. Porphyromonas gingivalis lipopolysaccharide (LPS) treatment strongly induced ANGPTL2 mRNA and protein levels in Ca9-22 human gingival epithelial cells. Recombinant human ANGPTL2 increased interleukin 1β (IL-1β), IL-8, and tumor necrosis factor-α (TNF-α) mRNA and protein levels in Ca9-22 cells. Small-interfering (si)RNA-mediated ANGPTL2 knockdown in Ca9-22 cells reduced IL-1β, IL-8 and TNF-α mRNA and protein levels compared with control siRNA (p<0.01) in P. gingivalis LPS-stimulated Ca9-22 cells. Antibodies against integrin α5β1, an ANGPTL receptor, blocked induction of these inflammatory cytokines in P. gingivalis LPS-treated Ca9-22 cells, suggesting that secreted ANGPTL induces inflammatory cytokines in gingival epithelial cells via an autocrine loop. The classic sequential cascade of P. gingivalis LPS → inflammatory cytokine induction is well established. However, in the current study, we reveal a novel cascade comprising sequential P. gingivalis LPS → ANGPTL2 → integrin α5β1 → inflammatory cytokine induction, which might be responsible for inducing potent periodontal disorganization activity in gingival epithelial cells. Via this pathway, ANGPTL2 functions in the pathogenesis of periodontitis and contributes to prolonging chronic inflammation in patients with systemic disease.

  13. Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells

    PubMed Central

    Ohno, Tasuku; Hayashi, Jun-ichiro; Nishida, Eisaku; Goto, Hisashi; Sasaki, Yasuyuki; Kikuchi, Takeshi; Fukuda, Mitsuo; Hasegawa, Yoshiaki; Mogi, Makio; Mitani, Akio

    2017-01-01

    Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by inducing inflammation and angiogenesis. It is produced in infiltrating immune cells or resident cells, such as adipocytes, vascular endothelial cells, and tumor cells. We hypothesized that ANGPTL2 might play an important role as a unique mediator in both systemic and periodontal disease. We demonstrated an increased ANGPTL2 concentration in gingival crevicular fluid from chronic periodontitis patients. Porphyromonas gingivalis lipopolysaccharide (LPS) treatment strongly induced ANGPTL2 mRNA and protein levels in Ca9-22 human gingival epithelial cells. Recombinant human ANGPTL2 increased interleukin 1β (IL-1β), IL-8, and tumor necrosis factor-α (TNF-α) mRNA and protein levels in Ca9-22 cells. Small-interfering (si)RNA-mediated ANGPTL2 knockdown in Ca9-22 cells reduced IL-1β, IL-8 and TNF-α mRNA and protein levels compared with control siRNA (p<0.01) in P. gingivalis LPS-stimulated Ca9-22 cells. Antibodies against integrin α5β1, an ANGPTL receptor, blocked induction of these inflammatory cytokines in P. gingivalis LPS-treated Ca9-22 cells, suggesting that secreted ANGPTL induces inflammatory cytokines in gingival epithelial cells via an autocrine loop. The classic sequential cascade of P. gingivalis LPS → inflammatory cytokine induction is well established. However, in the current study, we reveal a novel cascade comprising sequential P. gingivalis LPS → ANGPTL2 → integrin α5β1 → inflammatory cytokine induction, which might be responsible for inducing potent periodontal disorganization activity in gingival epithelial cells. Via this pathway, ANGPTL2 functions in the pathogenesis of periodontitis and contributes to prolonging chronic inflammation in patients with systemic disease. PMID:28934245

  14. 33 CFR 138.40 - Forms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  15. 33 CFR 138.30 - General.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  16. 33 CFR 138.130 - Fees.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  17. 33 CFR 138.40 - Forms.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  18. 33 CFR 138.30 - General.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  19. 33 CFR 138.130 - Fees.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  20. 33 CFR 138.10 - Scope.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  1. 33 CFR 138.10 - Scope.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  2. 33 CFR 138.40 - Forms.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  3. 33 CFR 138.40 - Forms.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  4. 33 CFR 138.30 - General.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  5. 33 CFR 138.10 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  6. 33 CFR 138.130 - Fees.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  7. 33 CFR 138.130 - Fees.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  8. 33 CFR 138.30 - General.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  9. 33 CFR 138.30 - General.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  10. 33 CFR 138.40 - Forms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  11. 33 CFR 138.130 - Fees.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

  12. Mesoscale modeling of vacancy-mediated Si segregation near an edge dislocation in Ni under irradiation

    NASA Astrophysics Data System (ADS)

    Li, Zebo; Trinkle, Dallas R.

    2017-04-01

    We use a continuum method informed by transport coefficients computed using self-consistent mean field theory to model vacancy-mediated diffusion of substitutional Si solutes in FCC Ni near an a/2 [1 1 ¯0 ] (111 ) edge dislocation. We perform two sequential simulations: first under equilibrium boundary conditions and then under irradiation. The strain field around the dislocation induces heterogeneity and anisotropy in the defect transport properties and determines the steady-state vacancy and Si distributions. At equilibrium both vacancies and Si solutes diffuse to form Cottrell atmospheres with vacancies accumulating in the compressive region above the dislocation core while Si segregates to the tensile region below the core. Irradiation raises the bulk vacancy concentration, driving vacancies to flow into the dislocation core. The out-of-equilibrium vacancy fluxes drag Si atoms towards the core, causing segregation to the compressive region, despite Si being an oversized solute in Ni.

  13. Concise Syntheses of bis-Strychnos Alkaloids (-)-Sungucine, (-)-Isosungucine, and (-)-Strychnogucine B from (-)-Strychnine.

    PubMed

    Zhao, Senzhi; Teijaro, Christiana N; Chen, Heng; Sirasani, Gopal; Vaddypally, Shivaiah; Zdilla, Michael J; Dobereiner, Graham E; Andrade, Rodrigo B

    2016-08-08

    The first chemical syntheses of complex, bis-Strychnos alkaloids (-)-sungucine (1), (-)-isosungucine (2), and (-)-strychnogucine B (3) from (-)-strychnine (4) is reported. Key steps included (1) the Polonovski-Potier activation of strychnine N-oxide; (2) a biomimetic Mannich coupling to forge the signature C23-C5' bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH3 CN-mediated reduction to fashion the ethylidene moieties in 1-3. DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Vascular Endothelial Growth Factor Secretion by Nonmyocytes Modulates Connexin-43 Levels in Cardiac Organoids

    PubMed Central

    Iyer, Rohin K.; Odedra, Devang; Chiu, Loraine L.Y.; Vunjak-Novakovic, Gordana

    2012-01-01

    We previously showed that the sequential, but not simultaneous, culture of endothelial cells (ECs), fibroblasts (FBs), and cardiomyocytes (CMs) resulted in elongated, beating cardiac organoids. We hypothesized that the expression of Cx43 and contractile function are mediated by vascular endothelial growth factor (VEGF) released by nonmyocytes during the preculture period. Cardiac organoids (∼200 μm diameter) were cultivated in microchannels to enable rapid screening. Three experimental groups were formed: (i) Simultaneous Preculture (ECs+FBs for 48 h, followed by CMs), (ii) Sequential Preculture (ECs for 24 h, FBs for 24 h, followed by CMs), and (iii) Simultaneous Triculture (ECs+FBs+CMs). Controls included CMs only, FBs only, and ECs only groups, and preculture with ECs only or FBs only. The highest VEGF levels were found in the Preculture groups [Simultaneous Preculture, 8.9±2.7 ng/(mL·h−1); Sequential Preculture, 16.6±3.4 ng/(mL·h−1)], as compared with Simultaneous Triculture where VEGF was not detectable, as shown by enzyme-linked immunosorbent assay. Analytical flow cytometry showed that VEGFR2 was expressed by ECs (86%±2 VEGFR2+), FBs (44%±1 VEGFR2+), and CMs (49%±2 VEGFR2+), showing that all three cell types were capable of responding to changes in VEGF. Addition of anti-VEGF neutralizing IgG (0.4 μg/mL) to Simultaneous Preculture resulted in 3-fold decrease in Cx43 mRNA and 1.5-fold decrease in Cx43 protein, while Simultaneous Triculture supplemented with VEGF ligand (30 ng/mL) had a threefold increase in Cx43 mRNA and a twofold increase in Cx43 protein. Addition of a small molecule inhibitor of the VEGFR2 receptor (19.4 nM) to Sequential Preculture caused a 1.4-fold decrease in Cx43 mRNA and a 4.1-fold decrease in Cx43 protein. Cx43 was localized within CMs, and not within FBs or ECs. Enriched CM organoids and Sequential Preculture organoids grown in the presence of VEGFR2 inhibitor displayed low levels of Cx43 and poor functional properties. Taken together, these results suggest that endogenous VEGF-VEGFR2 signaling enhanced Cx43 expression and cardiac function in engineered cardiac organoids. PMID:22519405

  15. Plant stimulation of soil microbial community succession: how sequential expression mediates soil carbon stabilization and turnover

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

    Firestone, Mary

    2015-03-31

    It is now understood that most plant C is utilized or transformed by soil microorganisms en route to stabilization. Hence the composition of microbial communities that mediate decomposition and transformation of root C is critical, as are the metabolic capabilities of these communities. The change in composition and function of the C-transforming microbial communities over time in effect defines the biological component of soil C stabilization. Our research was designed to test 2 general hypotheses; the first two hypotheses are discussed first; H1: Root-exudate interactions with soil microbial populations results in the expression of enzymatic capacities for macromolecular, complex carbonmore » decomposition; and H2: Microbial communities surrounding roots undergo taxonomic succession linked to functional gene activities as roots grow, mature, and decompose in soil. Over the term of the project we made significant progress in 1) quantifying the temporal pattern of root interactions with the soil decomposing community and 2) characterizing the role of root exudates in mediating these interactions.« less

  16. Measurement and modelling of reactive transport in geological barriers for nuclear waste containment

    DOE PAGES

    Xiong, Qingrong; Joseph, Claudia; Schmeide, Katja; ...

    2015-10-26

    Compacted clays are considered as excellent candidates for barriers to radionuclide transport in future repositories for nuclear waste due to their very low hydraulic permeability. Diffusion is the dominant transport mechanism, controlled by a nano-scale pore system. Assessment of the clays' long-term containment function requires adequate modelling of such pore systems and their evolution. Existing characterisation techniques do not provide complete pore space information for effective modelling, such as pore and throat size distributions and connectivity. Special network models for reactive transport are proposed here using the complimentary character of the pore space and the solid phase. Here, this balancesmore » the insufficient characterisation information and provides the means for future mechanical–physical–chemical coupling. The anisotropy and heterogeneity of clays is represented using different length parameters and percentage of pores in different directions. Resulting networks are described as mathematical graphs with efficient discrete calculus formulation of transport. Opalinus Clay (OPA) is chosen as an example. Experimental data for the tritiated water (HTO) and U(VI) diffusion through OPA are presented. Calculated diffusion coefficients of HTO and uranium species are within the ranges of the experimentally determined data in different clay directions. This verifies the proposed pore network model and validates that uranium complexes are diffusing as neutral species in OPA. In the case of U(VI) diffusion the method is extended to account for sorption and convection. Finally, rather than changing pore radii by coarse grained mathematical formula, physical sorption is simulated in each pore, which is more accurate and realistic.« less

  17. Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

    PubMed

    Madhi, Shabir A; Violari, Avy; Klugman, Keith P; Lin, Gina; McIntyre, James A; von Gottberg, Anne; Jean-Philippe, Patrick; Cotton, Mark F; Adrian, Peter

    2011-09-16

    Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy. We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses. Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ≥ 8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rdPCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ≥ 8 than the effect of colonization on the lower proportion with antibody ≥ 0.35 μg/ml. Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Measurement and modelling of reactive transport in geological barriers for nuclear waste containment.

    PubMed

    Xiong, Qingrong; Joseph, Claudia; Schmeide, Katja; Jivkov, Andrey P

    2015-11-11

    Compacted clays are considered as excellent candidates for barriers to radionuclide transport in future repositories for nuclear waste due to their very low hydraulic permeability. Diffusion is the dominant transport mechanism, controlled by a nano-scale pore system. Assessment of the clays' long-term containment function requires adequate modelling of such pore systems and their evolution. Existing characterisation techniques do not provide complete pore space information for effective modelling, such as pore and throat size distributions and connectivity. Special network models for reactive transport are proposed here using the complimentary character of the pore space and the solid phase. This balances the insufficient characterisation information and provides the means for future mechanical-physical-chemical coupling. The anisotropy and heterogeneity of clays is represented using different length parameters and percentage of pores in different directions. Resulting networks are described as mathematical graphs with efficient discrete calculus formulation of transport. Opalinus Clay (OPA) is chosen as an example. Experimental data for the tritiated water (HTO) and U(vi) diffusion through OPA are presented. Calculated diffusion coefficients of HTO and uranium species are within the ranges of the experimentally determined data in different clay directions. This verifies the proposed pore network model and validates that uranium complexes are diffusing as neutral species in OPA. In the case of U(vi) diffusion the method is extended to account for sorption and convection. Rather than changing pore radii by coarse grained mathematical formula, physical sorption is simulated in each pore, which is more accurate and realistic.

  19. Inhibition of poly(ADP-ribose) polymerase-1 alters expression of mitochondria-related genes in PC12 cells: relevance to mitochondrial homeostasis in neurodegenerative disorders.

    PubMed

    Czapski, Grzegorz A; Cieślik, Magdalena; Wencel, Przemysław L; Wójtowicz, Sylwia; Strosznajder, Robert P; Strosznajder, Joanna B

    2018-02-01

    Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells. Moreover, the effect of PARP-1 inhibitor (PJ34) on cells subjected to Aβ oligomers (AβO) - evoked stress was analyzed. Our data demonstrated that inhibition of PARP-1 in PC12 cells enhanced the transcription of genes for antioxidative enzymes (Sod1, Gpx1, Gpx4), activated genes regulating mitochondrial fission/fusion (Mfn1, Mfn2, Dnm1l, Opa1, Fis1), subunits of ETC complexes (mt-Nd1, Sdha, mt-Cytb) and modulated expression of several TFs, enhanced Foxo1 and decreased Nrf1, Stat6, Nfkb1. AβO elevated free radicals concentration, decreased mitochondria membrane potential (MMP) and cell viability after 24h. Gene transcription was not affected by AβO after 24h, but was significantly downregulated after 96h. In AβO stress, PJ34 exerted stimulatory effect on expression of several genes (Gpx1, Gpx4, Opa1, Mfn2, Fis1 and Sdha), decreased transcription of numerous TFs (Nrf1, Tfam, Stat3, Stat6, Trp53, Nfkb1) and prevented oxidative stress. Our results indicated that PARP-1 inhibition significantly enhanced transcription of genes involved in antioxidative defense and in regulation of mitochondria function, but was not able to ameliorate cells viability affected by Aβ. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Sequential protein association with nascent 60S ribosomal particles.

    PubMed

    Saveanu, Cosmin; Namane, Abdelkader; Gleizes, Pierre-Emmanuel; Lebreton, Alice; Rousselle, Jean-Claude; Noaillac-Depeyre, Jacqueline; Gas, Nicole; Jacquier, Alain; Fromont-Racine, Micheline

    2003-07-01

    Ribosome biogenesis in eukaryotes depends on the coordinated action of ribosomal and nonribosomal proteins that guide the assembly of preribosomal particles. These intermediate particles follow a maturation pathway in which important changes in their protein composition occur. The mechanisms involved in the coordinated assembly of the ribosomal particles are poorly understood. We show here that the association of preribosomal factors with pre-60S complexes depends on the presence of earlier factors, a phenomenon essential for ribosome biogenesis. The analysis of the composition of purified preribosomal complexes blocked in maturation at specific steps allowed us to propose a model of sequential protein association with, and dissociation from, early pre-60S complexes for several preribosomal factors such as Mak11, Ssf1, Rlp24, Nog1, and Nog2. The presence of either Ssf1 or Nog2 in complexes that contain the 27SB pre-rRNA defines novel, distinct pre-60S particles that contain the same pre-rRNA intermediates and that differ only by the presence or absence of specific proteins. Physical and functional interactions between Rlp24 and Nog1 revealed that the assembly steps are, at least in part, mediated by direct protein-protein interactions.

  1. The Relationship between Authoritarian Leadership and Employees' Deviant Workplace Behaviors: The Mediating Effects of Psychological Contract Violation and Organizational Cynicism.

    PubMed

    Jiang, Hongyan; Chen, Yang; Sun, Peizhen; Yang, Jun

    2017-01-01

    This study investigated the relationship between authoritarian leadership and employees' deviant workplace behaviors (DWB), as well as the mediating effects of psychological contract violation and organizational cynicism. A cross-sectional survey was conducted among 391 manufacturing workers in a northern city of China. Structural equation modeling was performed to test the theory-driven models. The results showed that the relationship between authoritarian leadership and employees' DWB was mediated by organizational cynicism. Moreover, this relationship was also sequentially mediated by psychological contract violation and organizational cynicism. This research unveiled psychological contract violation and organizational cynicism as underlying mechanism that explained the link between authoritarian leadership and employees' DWB.

  2. The Synaptic Cell Adhesion Molecule, SynCAM1, Mediates Astrocyte-to-Astrocyte and Astrocyte-to-GnRH Neuron Adhesiveness in the Mouse Hypothalamus

    PubMed Central

    Sandau, Ursula S.; Mungenast, Alison E.; McCarthy, Jack; Biederer, Thomas; Corfas, Gabriel

    2011-01-01

    We previously identified synaptic cell adhesion molecule 1 (SynCAM1) as a component of a genetic network involved in the hypothalamic control of female puberty. Although it is well established that SynCAM1 is a synaptic adhesion molecule, its contribution to hypothalamic function is unknown. Here we show that, in addition to the expected neuronal localization illustrated by its presence in GnRH neurons, SynCAM1 is expressed in hypothalamic astrocytes. Cell adhesion assays indicated that SynCAM is recognized by both GnRH neurons and astrocytes as an adhesive partner and promotes cell-cell adhesiveness via homophilic, extracellular domain-mediated interactions. Alternative splicing of the SynCAM1 primary mRNA transcript yields four mRNAs encoding membrane-spanning SynCAM1 isoforms. Variants 1 and 4 are predicted to be both N and O glycosylated. Hypothalamic astrocytes and GnRH-producing GT1-7 cells express mainly isoform 4 mRNA, and sequential N- and O-deglycosylation of proteins extracted from these cells yields progressively smaller SynCAM1 species, indicating that isoform 4 is the predominant SynCAM1 variant expressed in astrocytes and GT1-7 cells. Neither cell type expresses the products of two other SynCAM genes (SynCAM2 and SynCAM3), suggesting that SynCAM-mediated astrocyte-astrocyte and astrocyte-GnRH neuron adhesiveness is mostly mediated by SynCAM1 homophilic interactions. When erbB4 receptor function is disrupted in astrocytes, via transgenic expression of a dominant-negative erbB4 receptor form, SynCAM1-mediated adhesiveness is severely compromised. Conversely, SynCAM1 adhesive behavior is rapidly, but transiently, enhanced in astrocytes by ligand-dependent activation of erbB4 receptors, suggesting that erbB4-mediated events affecting SynCAM1 function contribute to regulate astrocyte adhesive communication. PMID:21486931

  3. 33 CFR 138.15 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

  4. 33 CFR 138.15 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

  5. 33 CFR 138.15 - Applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

  6. 33 CFR 138.15 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

  7. 33 CFR 138.15 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

  8. Fractalkine and CX3CR1 Mediate a Novel Mechanism of Leukocyte Capture, Firm Adhesion, and Activation under Physiologic Flow

    PubMed Central

    Fong, Alan M.; Robinson, Lisa A.; Steeber, Douglas A.; Tedder, Thomas F.; Yoshie, Osamu; Imai, Toshio; Patel, Dhavalkumar D.

    1998-01-01

    Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood mononuclear cells at physiologic wall shear stresses and induced firm adhesion of resting monocytes, resting and interleukin (IL)-2–activated CD8+ T lymphocytes and IL-2–activated NK cells. FKN also induced cell shape change in firmly adherent monocytes and IL-2–activated lymphocytes. CX3CR1-transfected K562 cells, but not control K562 cells, firmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor α–activated human umbilical vein endothelial cells. This firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-independent firm adhesion, and activation of circulating leukocytes under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte trafficking. PMID:9782118

  9. Supervisory Control of the Right Arm of the Beam Assembly Teleoperator.

    DTIC Science & Technology

    1985-05-10

    22332 L pQ5)1OLLA, Fg & E AND ADDRESS 12. REPORT DATE ATTN: DAPC-OPA-E 10 May 85 200 Stovall Street 13 NUMBEROF PAGES tf1 Alexandria. V4rqi nia 22332 171...MODUOE MOO FIGURE~ I. RgTArSuste -ll7- DC MOTOR END EFFECTOR FOR ROLLER SMALL POWER MODULE SOLENOID VALVE BOX MAIN POWER FIGURE A.6 Left Arm Subsystem...closed pneumatically. It is controlled by the ICS through the solenoid valve box and the RRT. At the base of the end effector is a roller. This roller

  10. Long-term study of ovine pulmonary adenocarcinogenesis in sheep with marginal vs. sufficient nutritional selenium supply: results from computed tomography, pathology, immunohistochemistry, JSRV-PCR and lung biochemistry.

    PubMed

    Humann-Ziehank, Esther; Renko, Kostja; Bruegmann, Michael L; Devi, Vemuri Rama; Hewicker-Trautwein, Marion; Andreae, Arnim; Ganter, Martin

    2013-10-01

    The impact of selenium (Se) in carcinogenesis is still debatable due to inconsistent results of observational studies, recent suspicion of diabetic side effects and e.g. dual roles of glutathione peroxidases (GPx). Previously, our group introduced long-term studies on lung carcinogenesis using the jaagtsiekte sheep retrovirus (JSRV) induced ovine pulmonary adenocarcinoma (OPA) as an innovative animal model. The present report describes the results of sufficient (0.2 mg Se/kg dry weight (dw)) vs. marginal (<0.05 mg Se/kg dw) nutritional Se supply on cancer progression over a two-year period in 16 animals. Computed tomography (CT) evaluation of lung cancer progression, final pathological examination, evidence of pro-viral JSRV-DNA in lung, lymph nodes and broncho-alveolar lavage cells as well as biochemical analysis of Se, GPx1 and thioredoxin reductase (TrxR) activity in lung tissue were recorded. Additionally, immunohistochemical determination of GPx1 expression in unaffected and neoplastic lung cells was implemented. The feeding regime caused significant differences in Se concentration and GPx1 activity in lung tissue between groups, whereas TrxR activity remained unaffected. JSRV was evident in broncho-alveolar lavage cells, lung tissue and lung lymph nodes. Quarterly executed CT could not demonstrate differences in lung cancer proliferation intensity. Necropsy and histopathology substantiated CT findings. Immunohistochemical analysis of GPx1 in lung tissue suggested a coherency of GPx1 immunolabelling intensity in dependence of tumour size. It was concluded that the model proved to be suitable for long-term studies of lung cancer proliferation including the impact of modifiable nutritional factors. Proliferation of OPA was unaffected by marginal vs. sufficient nutritional Se supply. Copyright © 2013 Elsevier GmbH. All rights reserved.

  11. Ontogeny of muscle bioenergetics in Adelie penguin chicks (Pygoscelis adeliae).

    PubMed

    Fongy, Anaïs; Romestaing, Caroline; Blanc, Coralie; Lacoste-Garanger, Nicolas; Rouanet, Jean-Louis; Raccurt, Mireille; Duchamp, Claude

    2013-11-01

    The ontogeny of pectoralis muscle bioenergetics was studied in growing Adélie penguin chicks during the first month after hatching and compared with adults using permeabilized fibers and isolated mitochondria. With pyruvate-malate-succinate or palmitoyl-carnitine as substrates, permeabilized fiber respiration markedly increased during chick growth (3-fold) and further rose in adults (1.4-fold). Several markers of muscle fiber oxidative activity (cytochrome oxidase, citrate synthase, hydroxyl-acyl-CoA dehydrogenase) increased 6- to 19-fold with age together with large rises in intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondrial content (3- to 5-fold) and oxidative activities (1.5- to 2.4-fold). The proportion of IMF relative to SS mitochondria increased with chick age but markedly dropped in adults. Differences in oxidative activity between mitochondrial fractions were reduced in adults compared with hatched chicks. Extrapolation of mitochondrial to muscle respirations revealed similar figures with isolated mitochondria and permeabilized fibers with carbohydrate-derived but not with lipid-derived substrates, suggesting diffusion limitations of lipid substrates with permeabilized fibers. Two immunoreactive fusion proteins, mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), were detected by Western blots on mitochondrial extracts and their relative abundance increased with age. Muscle fiber respiration was positively related with Mfn2 and OPA1 relative abundance. Present data showed by two complementary techniques large ontogenic increases in muscle oxidative activity that may enable birds to face thermal emancipation and growth in childhood and marine life in adulthood. The concomitant rise in mitochondrial fusion protein abundance suggests a role of mitochondrial networks in the skeletal muscle processes of bioenergetics that enable penguins to overcome harsh environmental constraints.

  12. High Level Ethanol from Sugar Cane Molasses by a New Thermotolerant Saccharomyces cerevisiae Strain in Industrial Scale.

    PubMed

    Fadel, M; Keera, Abeer A; Mouafi, Foukia E; Kahil, Tarek

    2013-01-01

    A new local strain of S. cerevisiae F-514, for ethanol production during hot summer season, using Egyptian sugar cane molasses was applied in Egyptian distillery factory. The inouluum was propagated through 300 L, 3 m(3), and 12 m(3) fermenters charged with diluted sugar cane molasses containing 4%-5% sugars. The yeast was applied in fermentation vessels 65 m(3) working volume to study the varying concentrations of urea, DAP, orthophosphoric acid (OPA), and its combinations as well as magnesium sulfate and inoculum size. The fermenter was allowed to stay for a period of 20 hours to give time for maximum conversion of sugars into ethanol. S. cerevisiae F-514 at molasses sugar level of 18% (w/v), inoculum size of 20% (v/v) cell concentration of 3.0 × 10(8)/mL, and combinations of urea, diammonium phosphate (DAP), orthophosphoric acid (OPA), and magnesium sulfate at amounts of 20, 10, 5, and 10 kg/65 m(3) working volume fermenters, respectively, supported maximum ethanol production (9.8%, v/v), fermentation efficiency (FE) 88.1%, and remaining sugars (RS) 1.22%. The fermentation resulted 13.4 g dry yeast/L contained 34.6% crude protein and 8.2% ash. By selecting higher ethanol yielding yeast strain and optimizing, the fermentation parameters both yield and economics of the fermentation process can be improved.

  13. Ozone-initiated chemistry in an occupied simulated aircraft cabin.

    PubMed

    Weschler, Charles J; Wisthaler, Armin; Cowlin, Shannon; Tamás, Gyöngyi; Strøm-Tejsen, Peter; Hodgson, Alfred T; Destaillats, Hugo; Herrington, Jason; Zhang, Junfeng; Nazaroff, William W

    2007-09-01

    We have used multiple analytical methods to characterize the gas-phase products formed when ozone was added to cabin air during simulated 4-hour flights that were conducted in a reconstructed section of a B-767 aircraft containing human occupants. Two separate groups of 16 females were each exposed to four conditions: low air exchange (4.4 (h-1)), <2 ppb ozone; low air exchange, 61-64 ppb ozone; high air exchange (8.8 h(-1)), <2 ppb ozone; and high air exchange, 73-77 ppb ozone. The addition of ozone to the cabin air increased the levels of identified byproducts from approximately 70 to 130 ppb at the lower air exchange rate and from approximately 30 to 70 ppb at the higher air exchange rate. Most of the increase was attributable to acetone, nonanal, decanal, 4-oxopentanal (4-OPA), 6-methyl-5-hepten-2-one (6-MHO), formic acid, and acetic acid, with 0.25-0.30 mol of quantified product volatilized per mol of ozone consumed. Several of these compounds reached levels above their reported odor thresholds. Most byproducts were derived from surface reactions with occupants and their clothing, consistent with the inference that occupants were responsible for the removal of >55% of the ozone in the cabin. The observations made in this study have implications for other indoor settings. Whenever human beings and ozone are simultaneously present, one anticipates production of acetone, nonanal, decanal, 6-MHO, geranyl acetone, and 4-OPA.

  14. Immunogenicity and persistence of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) in patients with untreated Smoldering Multiple Myeloma (SMM): A pilot study.

    PubMed

    Bahuaud, Mathilde; Bodilis, Hélène; Malphettes, Marion; Maugard Landre, Anaïs; Matondo, Caroline; Bouscary, Didier; Batteux, Frédéric; Launay, Odile; Fermand, Jean-Paul

    2017-11-01

    Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA). The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month. At 1 month post vaccination, 12 patients (60%) were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total) of the 12 responders had persistent immunity, and only 2 (10% of total) at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination. Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection.

  15. Org-1 is required for the diversification of circular visceral muscle founder cells and normal midgut morphogenesis

    PubMed Central

    Schaub, Christoph; Frasch, Manfred

    2013-01-01

    The T-Box family of transcription factors plays fundamental roles in the generation of appropriate spatial and temporal gene expression profiles during cellular differentiation and organogenesis in animals. In this study we report that the Drosophila Tbx1 orthologue optomotor-blind-related-gene-1 (org-1) exerts a pivotal function in the diversification of circular visceral muscle founder cell identities in Drosophila. In embryos mutant for org-1, the specification of the midgut musculature per se is not affected, but the differentiating midgut fails to form the anterior and central midgut constrictions and lacks the gastric caeca. We demonstrate that this phenotype results from the nearly complete loss of the founder cell specific expression domains of several genes known to regulate midgut morphogenesis, including odd-paired (opa), teashirt (tsh), Ultrabithorax (Ubx), decapentaplegic (dpp) and wingless (wg). To address the mechanisms that mediate the regulatory inputs from org-1 towards Ubx, dpp, and wg in these founder cells we genetically dissected known visceral mesoderm specific cis-regulatory-modules (CRMs) of these genes. The analyses revealed that the activities of the dpp and wg CRMs depend on org-1, the CRMs are bound by Org-1 in vivo and their T-Box binding sites are essential for their activation in the visceral muscle founder cells. We conclude that Org-1 acts within a well-defined signaling and transcriptional network of the trunk visceral mesoderm as a crucial founder cell-specific competence factor, in concert with the general visceral mesodermal factor Biniou. As such, it directly regulates several key genes involved in the establishment of morphogenetic centers along the anteroposterior axis of the visceral mesoderm, which subsequently organize the formation of midgut constrictions and gastric caeca and thereby determine the morphology of the midgut. PMID:23380635

  16. The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

    PubMed Central

    Rhodes, Lesley E.; Gledhill, Karl; Masoodi, Mojgan; Haylett, Ann K.; Brownrigg, Margaret; Thody, Anthony J.; Tobin, Desmond J.; Nicolaou, Anna

    2009-01-01

    Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE2, PGF2α, and PGE3 accompany the erythema in the first 24–48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.—Rhodes, L. E., Gledhill, K., Masoodi, M., Haylett, A. K., Brownrigg, M., Thody, A. J., Tobin, D. J., Nicolaou, A. The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases. PMID:19584301

  17. Mild and General Access to Diverse 1H-Benzotriazoles via Diboron-Mediated N-OH Deoxygenation and Palladium-Catalyzed C-C and C-N Bond Formation.

    PubMed

    Gurram, Venkateshwarlu; Akula, Hari K; Garlapati, Ramesh; Pottabathini, Narender; Lakshman, Mahesh K

    2015-02-09

    Benzotriazoles are a highly important class of compounds with broad-ranging applications in such diverse areas as medicinal chemistry, as auxiliaries in organic synthesis, in metallurgical applications, in aircraft deicing and brake fluids, and as antifog agents in photography. Although there are numerous approaches to N-substituted benzotriazoles, the essentially one general method to N-unsubstituted benzotriazoles is via diazotization of o -phenylenediamines, which can be limited by the availability of suitable precursors. Other methods to N-unsubstitued benzotriazoles are quite specialized. Although reduction of 1-hydroxy-1 H -benzotriazoles is known the reactions are not particularly convenient or broadly applicable. This presents a limitation for easy access to and availability of diverse benzotriazoles. Herein, we demonstrate a new, broadly applicable method to diverse 1 H -benzotriazoles via a mild diboron-reagent mediated deoxygenation of 1-hydroxy-1 H -benzotriazoles. We have also evaluated sequential deoxygenation and Pd-mediated C-C and C-N bond formation as a one-pot process for further diversification of the benzotriazole moiety. However, results indicated that purification of the deoxygenation product prior to the Pd-mediated reaction is critical to the success of such reactions. The overall chemistry allows for facile access to a variety of new benzotriazoles. Along with the several examples presented, a discussion of the advantages of the approaches is described, as also a possible mechanism for the deoxygenation process.

  18. Mild and General Access to Diverse 1H-Benzotriazoles via Diboron-Mediated N–OH Deoxygenation and Palladium-Catalyzed C–C and C–N Bond Formation

    PubMed Central

    Gurram, Venkateshwarlu; Akula, Hari K.; Garlapati, Ramesh; Pottabathini, Narender; Lakshman, Mahesh K.

    2015-01-01

    Benzotriazoles are a highly important class of compounds with broad-ranging applications in such diverse areas as medicinal chemistry, as auxiliaries in organic synthesis, in metallurgical applications, in aircraft deicing and brake fluids, and as antifog agents in photography. Although there are numerous approaches to N-substituted benzotriazoles, the essentially one general method to N-unsubstituted benzotriazoles is via diazotization of o-phenylenediamines, which can be limited by the availability of suitable precursors. Other methods to N-unsubstitued benzotriazoles are quite specialized. Although reduction of 1-hydroxy-1H-benzotriazoles is known the reactions are not particularly convenient or broadly applicable. This presents a limitation for easy access to and availability of diverse benzotriazoles. Herein, we demonstrate a new, broadly applicable method to diverse 1H-benzotriazoles via a mild diboron-reagent mediated deoxygenation of 1-hydroxy-1H-benzotriazoles. We have also evaluated sequential deoxygenation and Pd-mediated C–C and C–N bond formation as a one-pot process for further diversification of the benzotriazole moiety. However, results indicated that purification of the deoxygenation product prior to the Pd-mediated reaction is critical to the success of such reactions. The overall chemistry allows for facile access to a variety of new benzotriazoles. Along with the several examples presented, a discussion of the advantages of the approaches is described, as also a possible mechanism for the deoxygenation process. PMID:25729343

  19. 33 CFR 138.90 - Individual and Fleet Certificates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.90 Individual and Fleet Certificates. (a) The Director, NPFC...

  20. 33 CFR 138.120 - Certificates, denial or revocation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.120 Certificates, denial or revocation. (a) The Director, NPFC...

  1. 33 CFR 138.80 - Financial responsibility, how established.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.80 Financial responsibility, how established. (a) General. In...

  2. 33 CFR 138.140 - Enforcement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.140 Enforcement. (a) Any person who fails to comply with this subpart with respect...

  3. 33 CFR 138.140 - Enforcement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.140 Enforcement. (a) Any person who fails to comply with this subpart with respect...

  4. 33 CFR 138.120 - Certificates, denial or revocation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.120 Certificates, denial or revocation. (a) The Director, NPFC...

  5. 33 CFR 138.100 - Non-owning operator's responsibility for identification.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.100 Non-owning operator's...

  6. 33 CFR 138.65 - Issuance of Certificates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water... Responsibility (Water Pollution) (Form CG-5585) in electronic form. Copies of the Certificate may be downloaded...

  7. 33 CFR 138.100 - Non-owning operator's responsibility for identification.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.100 Non-owning operator's...

  8. 33 CFR 138.90 - Individual and Fleet Certificates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.90 Individual and Fleet Certificates. (a) The Director, NPFC...

  9. 33 CFR 138.140 - Enforcement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.140 Enforcement. (a) Any person who fails to comply with this subpart with respect...

  10. 33 CFR 138.120 - Certificates, denial or revocation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.120 Certificates, denial or revocation. (a) The Director, NPFC...

  11. 33 CFR 138.65 - Issuance of Certificates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water... Responsibility (Water Pollution) (Form CG-5585) in electronic form. Copies of the Certificate may be downloaded...

  12. 33 CFR 138.65 - Issuance of Certificates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water... Responsibility (Water Pollution) (Form CG-5585) in electronic form. Copies of the Certificate may be downloaded...

  13. 33 CFR 138.100 - Non-owning operator's responsibility for identification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.100 Non-owning operator's...

  14. 33 CFR 138.120 - Certificates, denial or revocation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.120 Certificates, denial or revocation. (a) The Director, NPFC...

  15. 33 CFR 138.140 - Enforcement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.140 Enforcement. (a) Any person who fails to comply with this subpart with respect...

  16. 33 CFR 138.90 - Individual and Fleet Certificates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.90 Individual and Fleet Certificates. (a) The Director, NPFC...

  17. 33 CFR 138.100 - Non-owning operator's responsibility for identification.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.100 Non-owning operator's...

  18. 33 CFR 138.80 - Financial responsibility, how established.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.80 Financial responsibility, how established. (a) General. In...

  19. 33 CFR 138.90 - Individual and Fleet Certificates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.90 Individual and Fleet Certificates. (a) The Director, NPFC...

  20. 33 CFR 138.65 - Issuance of Certificates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water... Responsibility (Water Pollution) (Form CG-5585) in electronic form. Copies of the Certificate may be downloaded...

  1. 33 CFR 138.65 - Issuance of Certificates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water... Responsibility (Water Pollution) (Form CG-5585) in electronic form. Copies of the Certificate may be downloaded...

  2. 33 CFR 138.120 - Certificates, denial or revocation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.120 Certificates, denial or revocation. (a) The Director, NPFC...

  3. 33 CFR 138.100 - Non-owning operator's responsibility for identification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.100 Non-owning operator's...

  4. 33 CFR 138.90 - Individual and Fleet Certificates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.90 Individual and Fleet Certificates. (a) The Director, NPFC...

  5. 33 CFR 138.140 - Enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.140 Enforcement. (a) Any person who fails to comply with this subpart with respect...

  6. Shift work and hypertension: Prevalence and analysis of disease pathways in a German car manufacturing company.

    PubMed

    Ohlander, Johan; Keskin, Mekail-Cem; Stork, Joachim; Radon, Katja

    2015-05-01

    Hypertension and cardiovascular disease (CVD) may share a similar pathophysiology. Despite shift workers' CVD excess risk, studies on shift work and hypertension are inconclusive. Blood pressure and shift status for 25,343 autoworkers were obtained from medical check-ups and company registers. Cross-sectional associations modeling the total effect from shift work (day shifts, shift work without nights, rotating shift work with nights, and night shifts) on hypertension were assessed. By sequential adjustments, the influence of behavioral, psychosocial, and physiological factors on the total effect was examined, with subsequent mediation and moderation analyses. Adjusted for confounders, shift work without nights (vs. day shifts) was significantly associated with hypertension (OR 1.15, 95%CI 1.02-1.30). The total effect was mediated by BMI, physical inactivity, and sleep disorders. No moderation of the total effect by behaviors was found. The association between shift work and hypertension seems mainly attributable to behavioral mechanisms. © 2015 Wiley Periodicals, Inc.

  7. Mitochondrial dysfunction in H9c2 cells during ischemia and amelioration with Tribulus terrestris L.

    PubMed

    Reshma, P L; Sainu, Neethu S; Mathew, Anil K; Raghu, K G

    2016-05-01

    The present study investigates the protective effect of partially characterized Tribulus terrestris L. fruit methanol extract against mitochondrial dysfunction in cell based (H9c2) myocardial ischemia model. To induce ischemia, the cells were maintained in an ischemic buffer (composition in mM -137 NaCl, 12 KCl, 0.5 MgCl2, 0.9 CaCl2, 20 HEPES, 20 2-deoxy-d-glucose, pH-6.2) at 37°C with 0.1% O2, 5% CO2, and 95% N2 in a hypoxia incubator for 1h. Cells were pretreated with various concentrations of T. terrestris L. fruit methanol extract (10 and 25μg/ml) and Cyclosporin A (1μM) for 24h prior to the induction of ischemia. Different parameters like lactate dehydrogenase release, total antioxidant capacity, glutathione content and antioxidant enzymes were investigated. Studies were conducted on mitochondria by analyzing alterations in mitochondrial membrane potential, integrity, and dynamics (fission and fusion proteins - Mfn1, Mfn2, OPA1, Drp1 and Fis1). Various biochemical processes in mitochondria like activity of electron transport chain (ETC) complexes, oxygen consumption and ATP production was measured. Ischemia for 1h caused a significant (p≤0.05) increase in LDH leakage, decrease in antioxidant activity and caused mitochondrial dysfunction. T. terrestris L. fruit methanol extract pretreatment was found effective in safeguarding mitochondria via its antioxidant potential, mediated through various bioactives. HPLC of T. terrestris L. fruit methanol extract revealed the presence of ferulic acid, phloridzin and diosgenin. T. terrestris L. fruit ameliorate ischemic insult in H9c2 cells by safeguarding mitochondrial function. This validates the use of T. terrestris L. against heart disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Loss of Mitofusin 2 Promotes Endoplasmic Reticulum Stress*

    PubMed Central

    Ngoh, Gladys A.; Papanicolaou, Kyriakos N.; Walsh, Kenneth

    2012-01-01

    The outer mitochondrial membrane GTPase mitofusin 2 (Mfn2) is known to regulate endoplasmic reticulum (ER) shape in addition to its mitochondrial fusion effects. However, its role in ER stress is unknown. We report here that induction of ER stress with either thapsigargin or tunicamycin in mouse embryonic fibroblasts leads to up-regulation of Mfn2 mRNA and protein levels with no change in the expression of the mitochondrial shaping factors Mfn1, Opa1, Drp1, and Fis1. Genetic deletion of Mfn2 but not Mfn1 in mouse embryonic fibroblasts or cardiac myocytes in mice led to an increase in the expression of the ER chaperone proteins. Genetic ablation of Mfn2 in mouse embryonic fibroblasts amplified ER stress and exacerbated ER stress-induced apoptosis. Deletion of Mfn2 delayed translational recovery through prolonged eIF2α phosphorylation associated with decreased GADD34 and p58IPK expression and elevated C/EBP homologous protein induction at late time points. These changes in the unfolded protein response were coupled to increased cell death reflected by augmented caspase 3/7 activity, lactate dehydrogenase release from cells, and an increase in propidium iodide-positive nuclei in response to thapsigargin or tunicamycin treatment. In contrast, genetic deletion of Mfn1 did not affect ER stress-mediated increase in ER chaperone synthesis or eIF2α phosphorylation. Additionally, ER stress-induced C/EBP homologous protein, GADD34, and p58IPK induction and cell death were not affected by loss of Mfn1. We conclude that Mfn2 but not Mfn1 is an ER stress-inducible protein that is required for the proper temporal sequence of the ER stress response. PMID:22511781

  9. IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway

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

    Ozeki, Nobuaki; Hase, Naoko; Hiyama, Taiki

    2014-10-15

    We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into α2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1β was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1β increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3more » mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1β-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1β-induced proliferation of ES cell-derived odontoblast-like cells. - Highlights: • IL-1β induces Wnt5, Lrp5/Fzd9 and MMP-3 in ES cell-derived odontoblast-like cells. • IL-1β-induced Wnt5 expression results in increased cell proliferation. • Exogenous Wnt5 increases MMP-3 activity and cell proliferation. • Exogenous Wnt5 rescues IL-1β-driven proliferation with anti-Wnt5 siRNA suppression. • IL-1β-induced cell proliferation involves Wnt5, Lrp5, and MMP-3 sequentially.« less

  10. Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis.

    PubMed

    Keller, Steve A; Paxian, Marcus; Lee, Sun M; Clemens, Mark G; Huynh, Toan

    2005-03-01

    Prostaglandins, synthesized by cyclooxygenase (COX), play an important role in the pathophysiology of inflammation. Severe injuries result in immunosuppression, mediated, in part, by maladaptive changes in macrophages. Herein, we assessed Kupffer cell-mediated cyclooxygenase-2 (COX-2) expression on liver function and damage after trauma and sepsis. To ablate Kupffer cells, Sprague Dawley rats were treated with gadolinium chloride (GdCl3) 48 and 24 h before experimentation. Animals then underwent femur fracture (FFx) followed 48 h later by cecal ligation and puncture (CLP). Controls received sham operations. After 24 h, liver samples were obtained, and mRNA and protein expression were determined by PCR, Western blot, and immunohistochemistry. Indocyanine-Green (ICG) clearance and plasma alanine aminotransferase (ALT) levels were determined to assess liver function and damage, respectively. One-way analysis of variance (ANOVA) with Student-Newman-Keuls test was used to assess statistical significance. After CLP alone, FFx+CLP, and GdCl3+FFx+CLP, clearance of ICG decreased. Plasma ALT levels increased in parallel with severity of injury. Kupffer cell depletion attenuated the increased ALT levels after FFx+CLP. Femur fracture alone did not alter COX-2 protein compared with sham. By contrast, COX-2 protein increased after CLP and was potentiated by sequential stress. Again, Kupffer cell depletion abrogated the increase in COX-2 after sequential stress. Immunohistochemical data confirmed COX-2 positive cells to be Kupffer cells. In this study, sequential stress increased hepatic COX-2 protein. Depletion of Kupffer cells reduced COX-2 and attenuated hepatocellular injuries. Our data suggest that Kupffer cell-dependent pathways may contribute to the inflammatory response leading to increased mortality after sequential stress.

  11. Parental perfectionism and overcontrol: examining mechanisms in the development of child anxiety.

    PubMed

    Affrunti, Nicholas W; Woodruff-Borden, Janet

    2015-04-01

    It has been theorized that perfectionistic parents will engage in behaviors characterized by overcontrol, which then increase child anxiety. Previous research has yet to test this theory within a single study. The current study investigated the proposed theory in a single model, examining the mediational roles of parent perfectionism and overcontrol in the association between parent and child anxiety. Participants were 77 parent-child dyads, with 46 parents and 40 children diagnosed with an anxiety disorder. Children were between 3 and 12 years old (57.1% female, 76.6% Caucasian, 22.1% African American). Path analysis indicated that the overall model fit the data well. Analyses showed that parental overcontrol mediated the relation between parental perfectionism and child anxiety and parental perfectionism mediated the relation between parental anxiety and parental overcontrol. Further, parental perfectionism and overcontrol sequentially mediated the parent to child anxiety relation. However, when parental perfectionism was accounted for in the model, parental overcontrol did not mediate the relation between parent and child anxiety. The findings suggest that parent perfectionism and overcontrol, together, may represent a specific pathway of risk for the development of anxiety disorders in children. The implications of these findings are reviewed in the context of previous theory on parental perfectionism, overcontrol, and the development of child anxiety. The clinical importance of the findings and future directions are also discussed.

  12. Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis

    PubMed Central

    Garg, Ankur; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven

    2017-01-01

    The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development. PMID:29028795

  13. Monitoring proteins using in vivo near-infrared time-domain optical imaging after 2-O-hexyldiglycerol-mediated transfer to the brain.

    PubMed

    Hülper, Petra; Dullin, Christian; Kugler, Wilfried; Lakomek, Max; Erdlenbruch, Bernhard

    2011-04-01

    The aim of the present study was to gain insight into the penetration, biodistribution, and fate of globulins in the brain after 2-O-hexyldiglycerol-induced blood-brain barrier opening. The spatial distribution of fluorescence probes was investigated after blood-brain barrier opening with intracarotid 2-O-hexyldiglycerol injection. Fluorescence intensity was visualized by microscopy (mice and rats) and by in vivo time-domain optical imaging. There was an increased 2-O-hexyldiglycerol-mediated transfer of fluorescence-labeled globulins into the ipsilateral hemisphere. Sequential in vivo measurements revealed that the increase in protein concentration lasted at least 96 h after administration. Ex vivo detection of tissue fluorescence confirmed the results obtained in vivo. Globulins enter the healthy brain in conjunction with 2-O-hexyldiglycerol. Sequential in vivo near-infrared fluorescence measurements enable the visualization of the spatial distribution of antibodies in the brain of living small animals.

  14. Income and children's behavioral functioning: a sequential mediation analysis.

    PubMed

    Shelleby, Elizabeth C; Votruba-Drzal, Elizabeth; Shaw, Daniel S; Dishion, Thomas J; Wilson, Melvin N; Gardner, Frances

    2014-12-01

    Children from low-income households tend to exhibit higher levels of conduct problems and emotional problems, yet the pathways linking economic disadvantage to children's behavioral functioning are not well understood. This study uses data from the Early Steps Multisite (ESM) project (N = 731) to investigate associations between family income in early childhood and children's conduct problems and emotional problems in middle childhood. The study explores whether the associations from income to child conduct problems and emotional problems operate through maternal depressive symptoms and 3 family risk factors in early childhood-harsh parenting, parenting hassles, and chaos in the home environment. Results of a sequential mediation model revealed significant indirect effects of family income on children's conduct problems operating through maternal depressive symptoms and parenting hassles and indirect effects of family income on children's emotional problems operating through maternal depressive symptoms, chaos in the home environment, and parenting hassles. Implications of these findings for understanding processes through which income influences child functioning are discussed.

  15. Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.

    PubMed

    Garg, Ankur; Bansal, Mukesh; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven; Zhang, Xin

    2017-10-01

    The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development.

  16. Imbalance of mitochondrial dynamics in Drosophila models of amyotrophic lateral sclerosis

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

    Altanbyek, Volodya; Cha, Sun-Joo; Kang, Ga-Un

    Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease, characterized by progressive and selective loss of motor neurons in the brain and spinal cord. DNA/RNA-binding proteins such as TDP-43, FUS, and TAF15 have been linked with the sporadic and familial forms of ALS. However, the exact pathogenic mechanism of ALS is still unknown. Recently, we found that ALS-causing genes such as TDP-43, FUS, and TAF15 genetically interact with mitochondrial dynamics regulatory genes. In this study, we show that mitochondrial fission was highly enhanced in muscles and motor neurons of TDP-43, FUS, and TAF15-induced fly models of ALS. Furthermore, themore » mitochondrial fission defects were rescued by co-expression of mitochondrial dynamics regulatory genes such as Marf, Opa1, and the dominant negative mutant form of Drp1. Moreover, we found that the expression level of Marf was decreased in ALS-induced flies. These results indicate that the imbalance of mitochondrial dynamics caused by instability of Marf is linked to the pathogenesis of TDP-43, FUS, and TAF15-associated ALS. - Highlights: • Mitochondrial fission is highly enhanced in TDP-43, FUS, and TAF15-induced fly models of ALS. • Excessive mitochondrial fragmentation in fly models of ALS is restored by mitochondrial dynamics regulatory genes. • Level of Marf protein is decreased in TDP-43, FUS, and TAF15-mediated ALS. • Imbalance of mitochondrial dynamics caused by Marf instability is linked to the pathogenesis of ALS.« less

  17. α2 Integrin, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-3 act sequentially to induce differentiation of mouse embryonic stem cells into odontoblast-like cells

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

    Ozeki, Nobuaki; Kawai, Rie; Hase, Naoko

    We previously reported that interleukin 1β acts via matrix metalloproteinase (MMP)-3 to regulate cell proliferation and suppress apoptosis in α2 integrin-positive odontoblast-like cells differentiated from mouse embryonic stem (ES) cells. Here we characterize the signal cascade underpinning odontoblastic differentiation in mouse ES cells. The expression of α2 integrin, extracellular matrix metalloproteinase inducer (Emmprin), and MMP-3 mRNA and protein were all potently increased during odontoblastic differentiation. Small interfering RNA (siRNA) disruption of the expression of these effectors potently suppressed the expression of the odontoblastic biomarkers dentin sialophosphoprotein, dentin matrix protein-1 and alkaline phosphatase, and blocked odontoblast calcification. Our siRNA, western blotmore » and blocking antibody analyses revealed a unique sequential cascade involving α2 integrin, Emmprin and MMP-3 that drives ES cell differentiation into odontoblasts. This cascade requires the interaction between α2 integrin and Emmprin and is potentiated by exogenous MMP-3. Finally, although odontoblast-like cells potently express α2, α6, αV, β1, and β3, integrins, we confirmed that β1 integrin acts as the trigger for ES cell differentiation, apparently in complex with α2 integrin. These results demonstrate a unique and unanticipated role for an α2 integrin-, Emmprin-, and MMP-3-mediated signaling cascade in driving mouse ES cell differentiation into odontoblast-like cells. - Highlights: • Odontoblast differentiation requires activation of α2 integrin, Emmprin and MMP-3. • α2 integrin, Emmprin and MMP-3 form a sequential signaling cascade. • β1 integrin acts a specific trigger for odontoblast differentiation. • The role of these effectors is highly novel and unanticipated.« less

  18. Emotional neglect in childhood shapes social dysfunctioning in adults by influencing the oxytocin and the attachment system: Results from a population-based study.

    PubMed

    Müller, Laura E; Bertsch, Katja; Bülau, Konstatin; Herpertz, Sabine C; Buchheim, Anna

    2018-06-01

    Early life maltreatment (ELM) is the major single risk factor for impairments in social functioning and mental health in adulthood. One of the most prevalent and most rapidly increasing forms of ELM is emotional neglect. According to bio-behavioral synchrony assumptions, the oxytocin and attachment systems play an important mediating role in the interplay between emotional neglect and social dysfunctioning. Therefore, the aim of the present study was to investigate whether fear and avoidance of social functioning, two important and highly prevalent facets of social dysfunctioning in adulthood, are shaped by emotional neglect, plasma oxytocin levels and attachment representations. We assessed emotional neglect as well as other forms of ELM with the Childhood Trauma Questionnaire, current attachment representations with the Adult Attachment Projective Picture System, and fear and avoidance of social situations with the Liebowitz Social Anxiety Scale in a population-based sample of N = 121 men and women. Furthermore, 4.9 ml blood samples were drawn from each participant to assess peripheral plasma oxytocin levels. Applying a sequential mediation model, results revealed that emotional neglect was associated with lower plasma oxytocin levels which in turn were associated with insecure attachment representations which were related to elevated fear and avoidance of social situations (a 1 d 21 b 2 : F 3,117  = 20.84, P < .001). Plasma oxytocin and current attachment representations hence fully and sequentially mediate the effects of emotional neglect on social fear and avoidance, two important facets of adult social dysfunctioning, confirming bio-behavioral synchrony assumptions. Copyright © 2018. Published by Elsevier B.V.

  19. Power Frequency Magnetic Fields Affect the p38 MAPK-Mediated Regulation of NB69 Cell Proliferation Implication of Free Radicals.

    PubMed

    Martínez, María Antonia; Úbeda, Alejandro; Moreno, Jorge; Trillo, María Ángeles

    2016-04-06

    The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38.

  20. Power Frequency Magnetic Fields Affect the p38 MAPK-Mediated Regulation of NB69 Cell Proliferation Implication of Free Radicals

    PubMed Central

    Martínez, María Antonia; Úbeda, Alejandro; Moreno, Jorge; Trillo, María Ángeles

    2016-01-01

    The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38. PMID:27058530

  1. USCG National Pollution Funds Center 1996 Annual Report

    DOT National Transportation Integrated Search

    1996-01-01

    The NPFC has fiduciary responsibility for the OSLTF and the portion of Superfund that the U.S. Coast Guard uses to respond to hazardous material releases in the U.S. coastal zones. In accordance with OPA and other pertinent laws and regulations, the ...

  2. 40 CFR 300.615 - Responsibilities of trustees.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 300.615 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY... trustees have the option of following the procedures for natural resource damage assessments located at 43...) In accordance with OPA section 1006(c), determine the need for assessment of natural resource damages...

  3. 33 CFR 138.70 - Renewal of Certificates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.70 Renewal of Certificates. (a) The operator of a vessel required to have a...

  4. 33 CFR 138.110 - Master Certificates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.110 Master Certificates. (a) A contractor or other person who is responsible for a...

  5. 33 CFR 138.110 - Master Certificates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.110 Master Certificates. (a) A contractor or other person who is responsible for a...

  6. 33 CFR 138.150 - Service of process.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.150 Service of process. (a) When executing the forms required by this subpart...

  7. 33 CFR 138.50 - Time to apply.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.50 Time to apply. (a) A vessel operator who wishes to obtain a Certificate must...

  8. 33 CFR 138.150 - Service of process.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.150 Service of process. (a) When executing the forms required by this subpart...

  9. 33 CFR 138.50 - Time to apply.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.50 Time to apply. (a) A vessel operator who wishes to obtain a Certificate must...

  10. 33 CFR 138.50 - Time to apply.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.50 Time to apply. (a) A vessel operator who wishes to obtain a Certificate must...

  11. 33 CFR 138.70 - Renewal of Certificates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.70 Renewal of Certificates. (a) The operator of a vessel required to have a...

  12. 33 CFR 138.150 - Service of process.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.150 Service of process. (a) When executing the forms required by this subpart...

  13. 33 CFR 138.110 - Master Certificates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.110 Master Certificates. (a) A contractor or other person who is responsible for a...

  14. 33 CFR 138.50 - Time to apply.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.50 Time to apply. (a) A vessel operator who wishes to obtain a Certificate must...

  15. 33 CFR 138.110 - Master Certificates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.110 Master Certificates. (a) A contractor or other person who is responsible for a...

  16. 33 CFR 138.150 - Service of process.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.150 Service of process. (a) When executing the forms required by this subpart...

  17. 33 CFR 138.70 - Renewal of Certificates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.70 Renewal of Certificates. (a) The operator of a vessel required to have a...

  18. 33 CFR 138.70 - Renewal of Certificates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.70 Renewal of Certificates. (a) The operator of a vessel required to have a...

  19. 33 CFR 138.50 - Time to apply.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.50 Time to apply. (a) A vessel operator who wishes to obtain a Certificate must...

  20. 33 CFR 138.70 - Renewal of Certificates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.70 Renewal of Certificates. (a) The operator of a vessel required to have a...

  1. 33 CFR 138.110 - Master Certificates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.110 Master Certificates. (a) A contractor or other person who is responsible for a...

  2. The Relationship between Authoritarian Leadership and Employees’ Deviant Workplace Behaviors: The Mediating Effects of Psychological Contract Violation and Organizational Cynicism

    PubMed Central

    Jiang, Hongyan; Chen, Yang; Sun, Peizhen; Yang, Jun

    2017-01-01

    This study investigated the relationship between authoritarian leadership and employees’ deviant workplace behaviors (DWB), as well as the mediating effects of psychological contract violation and organizational cynicism. A cross-sectional survey was conducted among 391 manufacturing workers in a northern city of China. Structural equation modeling was performed to test the theory-driven models. The results showed that the relationship between authoritarian leadership and employees’ DWB was mediated by organizational cynicism. Moreover, this relationship was also sequentially mediated by psychological contract violation and organizational cynicism. This research unveiled psychological contract violation and organizational cynicism as underlying mechanism that explained the link between authoritarian leadership and employees’ DWB. PMID:28536550

  3. Self-compassion and physical health: Exploring the roles of perceived stress and health-promoting behaviors

    PubMed Central

    Homan, Kristin J; Sirois, Fuschia M

    2017-01-01

    Growing evidence indicates that self-compassion is associated with better physical health, but the pathways that mediate this relationship are not well understood. This study tested a serial mediation model that linked self-compassion, perceived stress, health behaviors, and a comprehensive index of physical health. A sample of 176 individuals completed an online survey posted on Amazon’s Mechanical Turk. Self-compassion had an indirect effect on physical health via both mediators and through the sequential pathway, suggesting that taking a kind, accepting and mindful stance toward one’s flaws and failures may have benefits for reducing stress and promoting health behaviors. PMID:29379620

  4. High contrast research in the Nd:glass laser system based on optical parametric amplification temporal cleaning device

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoming; Leng, Yuxin; Sui, Zhan; Li, Yanyan; Zhang, Zongxin; Xu, Yi; Guo, Xiaoyang; Liu, Yanqi; Li, Ruxin; Xu, Zhizhan

    2014-02-01

    We demonstrate high amplified spontaneous emission (ASE) contrast pulses in a Nd:glass laser system based on the hybrid double chirped pulse amplification (double CPA) scheme. By an OPA temporal cleaning device, ~100 uJ/46 fs/ 1011 clean pulses are generated and amplified in the next Nd:glass laser. After compressor, >150 mJ/~0.5 ps/1 Hz pulses can be obtained. The ASE temporal contrast of amplified pulses is ~1011 with energy gain ~2.5×104 in the Nd:glass amplifiers.

  5. Concerted vs. Sequential. Two Activation Patterns of Vast Arrays of Intracellular Ca2+ Channels in Muscle

    PubMed Central

    Zhou, Jinsong; Brum, Gustavo; González, Adom; Launikonis, Bradley S.; Stern, Michael D.; Ríos, Eduardo

    2005-01-01

    To signal cell responses, Ca2+ is released from storage through intracellular Ca2+ channels. Unlike most plasmalemmal channels, these are clustered in quasi-crystalline arrays, which should endow them with unique properties. Two distinct patterns of local activation of Ca2+ release were revealed in images of Ca2+ sparks in permeabilized cells of amphibian muscle. In the presence of sulfate, an anion that enters the SR and precipitates Ca2+, sparks became wider than in the conventional, glutamate-based solution. Some of these were “protoplatykurtic” (had a flat top from early on), suggesting an extensive array of channels that activate simultaneously. Under these conditions the rate of production of signal mass was roughly constant during the rise time of the spark and could be as high as 5 μm3 ms−1, consistent with a release current >50 pA since the beginning of the event. This pattern, called “concerted activation,” was observed also in rat muscle fibers. When sulfate was combined with a reduced cytosolic [Ca2+] (50 nM) these sparks coexisted (and interfered) with a sequential progression of channel opening, probably mediated by Ca2+-induced Ca2+ release (CICR). Sequential propagation, observed only in frogs, may require parajunctional channels, of RyR isoform β, which are absent in the rat. Concerted opening instead appears to be a property of RyR α in the amphibian and the homologous isoform 1 in the mammal. PMID:16186560

  6. 'Sticking to a healthy diet is easier for me when I exercise regularly': cognitive transfer between physical exercise and healthy nutrition.

    PubMed

    Fleig, Lena; Kerschreiter, Rudolf; Schwarzer, Ralf; Pomp, Sarah; Lippke, Sonia

    2014-01-01

    Long-term rehabilitation success depends on regular exercise and healthy nutrition. The present study introduces a new framework to explain this association on a psychosocial level. The exercise-nutrition relationship was investigated by exploring the sequential mediation of habit strength and transfer cognitions. Analyses were performed at two measurement points in time (at 12 and 18 months after rehabilitation), involving 470 medical rehabilitation patients who participated in an exercise intervention. Patients filled in paper-pencil questionnaires assessing exercise (t1) and habit strength, transfer cognitions and healthy nutrition at follow-up (t2). Habit strength and transfer cognitions mediated the relationship between exercise and nutrition. Findings suggest that habit strength and transfer cognitions are important factors underlying the relationship between exercise and nutrition.

  7. Cone Beam Computed Tomography Analysis of Oropharyngeal Airway in Preadolescent Nonsyndromic Bilateral and Unilateral Cleft Lip and Palate Patients.

    PubMed

    Al-Fahdawi, Mahmood Abd; El-Kassaby, Marwa Abdelwahab; Farid, Mary Medhat; El-Fotouh, Mona Abou

    2018-01-01

    Objective The objective of this study was to assess the volume, area, and dimensions of the oropharyngeal airway (OPA) in a previously repaired nonsyndromic unilateral cleft lip and palate (UCLP) versus bilateral cleft lip and palate (BCLP) patients when compared with noncleft controls using cone beam computed tomography (CBCT). Design This was a retrospective case-control study. Setting The Cleft Care Center and outpatient clinic that are affiliated to our faculty were the settings for the study. Participants A total of 58 CBCT scans were selected of preadolescent individuals: 14 BCLP, 20 UCLP, and 24 age- and gender-matched noncleft controls. Variables Variables were volume, cross-sectional area (CSA), midsagittal area (MSA), and dimensions of OPA. Statistical analysis One-way analysis of variance and post hoc tests were used to compare variables. Statistical significance was set at P ≤ .05. Results UCLP showed significantly smaller superior oropharyngeal airway volume than both controls and BCLP ( P ≤ .05). BCLP showed significantly larger CSA at soft palate plane and significantly larger MSA than both UCLP and controls ( P < .05). Conclusions UCLP patients at the studied age and stage of previously repaired clefts have significantly less superior oropharyngeal airway volume than both controls and BCLP patients. This confirms that preadolescents with UCLP are at greater risk for superior oropharyngeal airway obstruction when compared with those BCLP and controls. Furthermore, BCLP patients showed significantly larger CSA at soft palate plane and MSA than both controls and UCLP patients. These variations in OPA characteristics of cleft patients can influence function in terms of respiration and vocalization.

  8. Dynamic Contour Tonometry (DCT) over a thin daily disposable hydrogel contact lens.

    PubMed

    Nosch, Daniela Sonja; Duddek, Armin P; Herrmann, Didier; Stuhrmann, Oliver M

    2010-10-01

    Dynamic Contour Tonometry (DCT) has been shown to measure the intraocular pressure (IOP) independent of corneal physical properties such as thickness, curvature and rigidity. The aim of this study was to find out if DCT remains accurate when it is applied on regularly shaped corneas while a thin, daily hydrogel contact lens (CL) is worn. This was a prospective, randomised study and included 46 patients (46 right eyes): 26 females and 20 males. The age varied from 22 to 66 years (mean: 43.0+/-12.70 years). IOP and ocular pulse amplitude (OPA) measurements were taken with and without a daily disposable hydrogel CL (-0.50 D), Filcon IV) in situ (using the DCT), with a randomised order of measurements. The average value for the IOP measurements without CL was 16.51+/-3.20 mmHg, and with CL in situ it was 16.10+/-3.10 mmHg. The mean difference was 0.41 mmHg and not found to be statistically significant (p=0.074). The average value for the OPA measurement without CL was 2.20+/-0.79 mmHg. With CL in situ it was 2.08+/-0.81 mmHg. This gave a mean difference of 0.11 mmHg and was statistically significant (p=0.025). The Bland-Altman plot showed a maximum difference in IOP of +2.44 and -2.00 mmHg (CI 0.95). Regarding OPA, the maximum difference was +0.81 and -0.60 mmHg (CI 0.95). The presence of a thin hydrogel CL did not affect the accuracy of IOP measurements using the DCT. The ocular pulse amplitude was measured on average 5.45% lower with a CL in situ. Copyright (c) 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  9. Extreme High and Low Temperature Operation of the Silicon-On-Insulator Type CHT-OPA Operational Amplifier

    NASA Technical Reports Server (NTRS)

    Patterson, Richard; Hammoud, Ahmad; Elbuluk, Malik

    2008-01-01

    A new operational amplifier chip based on silicon-on-insulator technology was evaluated for potential use in extreme temperature environments. The CHT-OPA device is a low power, precision operational amplifier with rail-to-rail output swing capability, and it is rated for operation between -55 C and +225 C. A unity gain inverting circuit was constructed utilizing the CHT-OPA chip and a few passive components. The circuit was evaluated in the temperature range from -190 C to +200 C in terms of signal gain and phase shift, and supply current. The investigations were carried out to determine suitability of this device for use in space exploration missions and aeronautic applications under wide temperature incursion. Re-restart capability at extreme temperatures, i.e. power switched on while the device was soaked at extreme temperatures, was also investigated. In addition, the effects of thermal cycling under a wide temperature range on the operation of this high performance amplifier were determined. The results from this work indicate that this silicon-on-insulator amplifier chip maintained very good operation between +200 C and -190 C. The limited thermal cycling had no effect on the performance of the amplifier, and it was able to re-start at both -190 C and +200 C. In addition, no physical degradation or packaging damage was introduced due to either extreme temperature exposure or thermal cycling. The good performance demonstrated by this silicon-on-insulator operational amplifier renders it a potential candidate for use in space exploration missions or other environments under extreme temperatures. Additional and more comprehensive characterization is, however, required to establish the reliability and suitability of such devices for long term use in extreme temperature applications.

  10. Comparison and Correlation of Neisseria meningitidis Serogroup B Immunologic Assay Results and Human Antibody Responses following Three Doses of the Norwegian Meningococcal Outer Membrane Vesicle Vaccine MenBvac

    PubMed Central

    Findlow, Jamie; Taylor, Stephen; Aase, Audun; Horton, Rachel; Heyderman, Robert; Southern, Jo; Andrews, Nick; Barchha, Rita; Harrison, Ewan; Lowe, Ann; Boxer, Emma; Heaton, Charlotte; Balmer, Paul; Kaczmarski, Ed; Oster, Philipp; Gorringe, Andrew; Borrow, Ray; Miller, Elizabeth

    2006-01-01

    The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease. PMID:16861642

  11. Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

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

    Liu, Penghao; Xie, Qihai; Wei, Tong

    Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in bothmore » strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.« less

  12. On the Fringe Field of Wide Angle LC Optical Phased Array

    NASA Technical Reports Server (NTRS)

    Wang, Xighua; Wang, Bin; Bos, Philip J.; Anderson, James E.; Pouch, John; Miranda, Felix; McManamon, Paul F.

    2004-01-01

    For free space laser communication, light weighted large deployable optics is a critical component for the transmitter. However, such an optical element will introduce large aberrations due to the fact that the surface figure of the large optics is susceptable to deformation in the space environment. We propose to use a high-resolution liquid crystal spatial light modulator to correct for wavefront aberrations introduced by the primary optical element, and to achieve very fine beam steering and shaping at the same time. A 2-D optical phased array (OPA) antenna based on a Liquid Crystal on Silicon (LCOS) spatial light modulator is described. This device offers a combination of low cost, high resolution, high accuracy, high diffraction efficiency at video speed. To quantitatively understand the influence factor of the different design parameters, a computer simulation of the device is given by the 2-D director simulation and the Finite Difference Time domain (FDTD) simulation. For the 1-D OPA, we define the maximum steering angle to have a grating period of 8 pixel/reset scheme; as for larger steering angles than this criterion, the diffraction efficiency drops dramatically. In this case, the diffraction efficiency of 0.86 and the Strehl ratio of 0.9 are obtained in the simulation. The performance of the device in achieving high resolution wavefront correction and beam steering is also characterized experimentally.

  13. Pathways to Hazardous Drinking Among Racially and Socioeconomically Diverse Lesbian Women: Sexual Minority Stress, Rumination, Social Isolation, and Drinking to Cope

    PubMed Central

    Lewis, Robin J.; Mason, Tyler B.; Winstead, Barbara A.; Gaskins, Melissa; Irons, Lance B.

    2016-01-01

    Lesbian women engage in more hazardous drinking than heterosexual women yet we know relatively little about what explains this disparity. In the present study, race, socioeconomic status, minority stress, general psychological processes and distress were examined as pathways to hazardous drinking among young (18-35 years) Black and non-Hispanic White lesbian women. We used the psychological mediation framework adaptation of minority stress theory and the reserve capacity model as theoretical underpinnings of the conceptual model in the current study. Self-identified lesbian participants (N= 867) completed a one-time online survey that assessed race, socioeconomic status, perceived sexual minority discrimination, proximal minority stress (concealment, internalized homophobia, lack of connection to lesbian community), rumination, social isolation, psychological distress, drinking to cope, and hazardous drinking. Cross-sectional results demonstrated that being Black was associated with hazardous drinking via sequential mediators of rumination, psychological distress, and drinking to cope. Socioeconomic status was associated with hazardous drinking via sequential mediators of sexual minority discrimination, proximal minority stress, rumination, social isolation, psychological distress, and drinking to cope. Understanding these pathways can aid researchers and clinicians studying and working with lesbians who are at risk for hazardous drinking. PMID:28138208

  14. Phytohormone mediation of interactions between herbivores and plant pathogens.

    PubMed

    Lazebnik, Jenny; Frago, Enric; Dicke, Marcel; van Loon, Joop J A

    2014-07-01

    Induced plant defenses against either pathogens or herbivore attackers are regulated by phytohormones. These phytohormones are increasingly recognized as important mediators of interactions between organisms associated with plants. In this review, we discuss the role of plant defense hormones in sequential tri-partite interactions among plants, pathogenic microbes, and herbivorous insects, based on the most recent literature. We discuss the importance of pathogen trophic strategy in the interaction with herbivores that exhibit different feeding modes. Plant resistance mechanisms also affect plant quality in future interactions with attackers. We discuss exemplary evidence for the hypotheses that (i) biotrophic pathogens can facilitate chewing herbivores, unless plants exhibit effector-triggered immunity, but (ii) facilitate or inhibit phloem feeders. (iii) Necrotrophic pathogens, on the other hand, can inhibit both phloem feeders and chewers. We also propose herbivore feeding mode as predictor of effects on pathogens of different trophic strategies, providing evidence for the hypotheses that (iv) phloem feeders inhibit pathogen attack by increasing SA induction, whereas (v) chewing herbivores tend not to affect necrotrophic pathogens, while they may either inhibit or facilitate biotrophic pathogens. Putting these hypotheses to the test will increase our understanding of phytohormonal regulation of plant defense to sequential attack by plant pathogens and insect herbivores. This will provide valuable insight into plant-mediated ecological interactions among members of the plant-associated community.

  15. 33 CFR 138.85 - Implementation schedule for amendments to applicable amounts by regulation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.85 Implementation schedule for...

  16. 33 CFR 138.85 - Implementation schedule for amendments to applicable amounts by regulation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.85 Implementation schedule for...

  17. 33 CFR 138.85 - Implementation schedule for amendments to applicable amounts by regulation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.85 Implementation schedule for...

  18. 33 CFR 138.85 - Implementation schedule for amendments to applicable amounts by regulation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.85 Implementation schedule for...

  19. 15 CFR 990.55 - Restoration selection-developing restoration plans.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Restoration selection-developing... POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Planning Phase § 990.55 Restoration selection—developing restoration plans. (a) General. OPA requires that damages be based upon a...

  20. 15 CFR 990.55 - Restoration selection-developing restoration plans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Restoration selection-developing... POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Planning Phase § 990.55 Restoration selection—developing restoration plans. (a) General. OPA requires that damages be based upon a...

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