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Sample records for residues disrupted association

  1. Mutations in non-acid patch residues disrupt H2A.Z's association with chromatin through multiple mechanisms.

    Directory of Open Access Journals (Sweden)

    Thomas J Wood

    Full Text Available The incorporation of histone variants into nucleosomes is a critical mechanism for regulating essential DNA-templated processes and for establishing distinct chromatin architectures with specialised functions. H2A.Z is an evolutionarily conserved H2A variant that has diverse roles in transcriptional regulation, heterochromatin boundary definition, chromosome stability and DNA repair. The H2A.Z C-terminus diverges in sequence from canonical H2A and imparts unique functions to H2A.Z in the yeast S. cerevisiae. Although mediated in part through the acid patch-containing M6 region, many molecular determinants of this divergent structure-function relationship remain unclear. Here, by using an unbiased random mutagenesis screen of H2A.Z alleles, we identify point mutations in the C-terminus outside of the M6 region that disrupt the normal function of H2A.Z in response to cytotoxic stress. These functional defects correlate with reduced chromatin association, which we attribute to reduced physical stability within chromatin, but also to altered interactions with the SWR and INO80 chromatin remodeling complexes. Together with experimental data, computational modelling of these residue changes in the context of protein structure suggests the importance of C-terminal domain integrity and configuration for maintaining the level of H2A.Z in nucleosomes.

  2. National Defense Industrial Association Disruptive Technologies Conference

    Science.gov (United States)

    2009-10-14

    Algorithms, MEMS • Nano ; Meta; & New Materials • Cognitive Computing • Bio-Revolution NDIA Disruptive Technologies 10/16/2009 Page-8 Forces of Change...DISTRIBUTE 2 1 st Cen t u r y St r a t eg ic Tec h n o l o g y Vec t o r s Defense Science Board 2006 Summer Study August 18, 2006 (Final) NDIA

  3. Disruption?

    DEFF Research Database (Denmark)

    2016-01-01

    This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray......This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray...

  4. Impact-disrupted gunshot residue: A sub-micron analysis using a novel collection protocol

    Directory of Open Access Journals (Sweden)

    V. Spathis

    2017-06-01

    Full Text Available The analysis of gunshot residue (GSR has played an integral role within the legal system in relation to shooting cases. With a characteristic elemental composition of lead, antimony, barium, and a typically discriminative spheroidal morphology, the presence and distribution of GSR can aid in firearm investigations. In this experiment, three shots of low velocity rim-fire ammunition were fired over polished silicon collection substrates placed at six intervals over a 100 cm range. The samples were analysed using a Field Emission Gun Scanning Electron Microscope (FEG-SEM in conjunction with an X-flash Energy Dispersive X-ray (EDX detector, allowing for GSR particle analyses of composition and structure at the sub-micron level. The results of this experiment indicate that although classic spheroidal particles are present consistently throughout the entire range of samples their sizes vary significantly, and at certain distances from the firearm particles with an irregular morphology were discerned, forming “impact-disrupted” GSR particles, henceforth colloquially referred to as “splats”. Upon further analysis, trends with regards to the formation of these splat particles were distinguished. An increase in splat frequency was observed starting at 10 cm from the firearm, with 147 mm−2 splat density, reaching a maximal flux at 40 cm (451 mm−2, followed by a gradual decrease to the maximum range sampled. Moreover, the structural morphology of the splats changes throughout the sampling range. At the distances closest to the firearm, molten-looking particles were formed, demonstrating the metallic residues were in a liquid state when their flight path was disrupted. However, at increased distances-primarily where the discharge plume was at maximum dispersion and moving away from the firearm, the residues have had time to cool in-fight resulting in semi-congealed and solid particles that subsequently disrupted upon impact, forming more

  5. [Vascular disruption birth defects are not associated to chromosomal alterations].

    Science.gov (United States)

    Pachajoa, Harry; Ariza, Yoseth; Isaza, Carolina; Méndez, Fabián

    2015-11-01

    It is estimated that 2 to 35 of newborns present a congenital malformation. Some publications suggest that vascular disruption birth defects are not associated with chromosomal alterations detected by conventional karyotype. to determine the frequency of chromosomal alterations detected by high resolution G banded karyotype in patients with vascular disruption birth defects in a Colombian population (South America). transversal study. Population: a sample of patients identified by an epidemiological surveillance system of congenital malformations in a reference hospital in Cali, Colombia. 41 cases of vascular disruption birth defects were identified during a 36 month period; in a descending order those were: transverse reduction defects, hydranencephaly and gastroschisis. Two expert cytogenetists performed independent evaluation of the genetic material of the patients, and no chromosomal alterations detectable by G banded karyotype were identified. It is recommended that genetic counseling in cases of defects by vascular disruption is carried out taking into account the empirical recurrence risks reported for each one the types of defects by vascular disruption and the use of karyotype should be limited to cases with other malformations or chromosomal abnormality suspected by phenotype.

  6. The association of telomere length with family violence and disruption.

    Science.gov (United States)

    Drury, Stacy S; Mabile, Emily; Brett, Zoë H; Esteves, Kyle; Jones, Edward; Shirtcliff, Elizabeth A; Theall, Katherine P

    2014-07-01

    To enhance the understanding of biological mechanisms connecting early adversity and negative health, we examine the association between family interpersonal violence and disruption and telomere length in youth. These specific exposures were selected because of their established links with negative health consequences across the life-course. Children, age 5 to 15, were recruited from the greater New Orleans area, and exposure to family disruption and violence was assessed through caregiver report. Telomere length, from buccal cell DNA (buccal telomere length [bTL]), was determined by using monochrome multiplex quantitative real-time polymerase chain reaction. The association between bTL and adversity exposure was tested (n = 80). Cumulative exposure to interpersonal violence and family disruption was correlated with bTL. Controlling for other sociodemographic factors, bTL was significantly shorter in children with higher exposure to family violence and disruption. Witnessing family violence exerted a particularly potent impact. A significant gender interaction was found (β = -0.0086, SE = 0.0031, z test= -2.79, P = .0053) and analysis revealed the effect only in girls. bTL is a molecular biomarker of adversity and allostatic load that is detectable in childhood. The present results extend previous studies by demonstrating that telomeres are sensitive to adversity within the overarching family domain. These findings suggest that the family ecology may be an important target for interventions to reduce the biological impact of adversity in the lives of children. Copyright © 2014 by the American Academy of Pediatrics.

  7. Endocrine-disrupting chemicals: associated disorders and mechanisms of action.

    Science.gov (United States)

    De Coster, Sam; van Larebeke, Nicolas

    2012-01-01

    The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

  8. Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Sam De Coster

    2012-01-01

    Full Text Available The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

  9. Disruption of conditioned reward association by typical and atypical antipsychotics.

    Science.gov (United States)

    Danna, C L; Elmer, G I

    2010-07-01

    Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward-predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100microg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3-30microg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward-predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward-predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward

  10. Associations for Disruptiveness: The Pirate Bay vs. Spotify

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    Bjorn Remneland Wikhamn

    2016-10-01

    Full Text Available Most studies on disruptive innovations adopt technology-centric assumptions when explaining how industries are affected by a technology’s creative destruction. This paper argues that the power of a technology lies in how it performatively associates with the cultural and social norms of the wider society. Hence, a technology is not disruptive or sustaining in itself but is potentially a productive outcome of network linkages with other social and material elements. To illustrate this claim, two digital music services will be analyzed, respectively a misfit and a maverick both challenging mainstream providers of music – The Pirate Bay and Spotify – in relation to each other and how they are positioned toward the transformation of the music industry as a whole.

  11. Longitudinal association between marital disruption and child BMI and obesity.

    Science.gov (United States)

    Arkes, Jeremy

    2012-08-01

    This research examines whether family disruptions (i.e., divorces and separation) contribute to children's weight problems. The sample consists of 7,299 observations for 2,333 children, aged 5-14, over the 1986-2006 period, from a US representative sample from the Child and Young Adult Survey accompanying the National Longitudinal Survey of Youth (NLSY). The study uses individual-fixed-effects models in a longitudinal framework to compare children's BMI and weight problems before and after a disruption. Furthermore, besides doing a before-after comparison for children, the study also estimates the effects at various periods relative to the disruption in order to examine whether children are affected before the disruption and whether any effects change as time passes from the disruption, as some effects may be temporary or slow to develop. Despite having a larger sample than the previous studies, the results provide no evidence that, on average, children's BMI and BMI percentile scores (measured with continuous outcomes) are affected before the disruption, after the disruption, and as time passes from the disruption, relative to a baseline period a few years before the disruption. However, children experiencing a family disruption do have an increased risk of obesity (having a BMI percentile score of 95 or higher) in the two years leading up to the disruption as well as after the disruption, and as time passes from the disruption.

  12. Sleep disruption and the sequelae associated with traumatic brain injury.

    Science.gov (United States)

    Lucke-Wold, Brandon P; Smith, Kelly E; Nguyen, Linda; Turner, Ryan C; Logsdon, Aric F; Jackson, Garrett J; Huber, Jason D; Rosen, Charles L; Miller, Diane B

    2015-08-01

    Sleep disruption, which includes a loss of sleep as well as poor quality fragmented sleep, frequently follows traumatic brain injury (TBI) impacting a large number of patients each year in the United States. Fragmented and/or disrupted sleep can worsen neuropsychiatric, behavioral, and physical symptoms of TBI. Additionally, sleep disruption impairs recovery and can lead to cognitive decline. The most common sleep disruption following TBI is insomnia, which is difficulty staying asleep. The consequences of disrupted sleep following injury range from deranged metabolomics and blood brain barrier compromise to altered neuroplasticity and degeneration. There are several theories for why sleep is necessary (e.g., glymphatic clearance and metabolic regulation) and these may help explain how sleep disruption contributes to degeneration within the brain. Experimental data indicate disrupted sleep allows hyperphosphorylated tau and amyloid β plaques to accumulate. As sleep disruption may act as a cellular stressor, target areas warranting further scientific investigation include the increase in endoplasmic reticulum and oxidative stress following acute periods of sleep deprivation. Potential treatment options for restoring the normal sleep cycle include melatonin derivatives and cognitive behavioral therapy. Published by Elsevier Ltd.

  13. Foster placement disruptions associated with problem behavior: mitigating a threshold effect.

    Science.gov (United States)

    Fisher, Philip A; Stoolmiller, Mike; Mannering, Anne M; Takahashi, Aiko; Chamberlain, Patricia

    2011-08-01

    Placement disruptions have adverse effects on foster children. Identifying reliable predictors of placement disruptions might assist in the allocation of services to prevent disruptions. There were two objectives in this study: (a) to replicate a prior finding that the number of daily child problem behaviors at entry into a new foster home predicts subsequent placement disruptions in foster preschoolers and (b) to determine whether this association is mitigated by a treatment foster care intervention. Problem behavior and placement disruptions were examined in 60 children in regular foster care (age range = 3.10-5.91 years [M = 4.34, SD = 0.83], 58.3% male, 93.4% Caucasian) and 57 children in a treatment foster care program (age range = 3.01-6.78 years [M = 4.54, SD = 0.86], 49.1% male, 82.5% Caucasian). Using the Parent Daily Report Checklist (Chamberlain & Reid, 1987), a brief telephone interview, foster caregivers reported problem behavior 6 times over 3 months. Placement disruptions were tracked over 12 months. The regular foster care children with 5 or fewer problem behaviors were at low risk for disruption, but their risk increased 10% for each additional behavior (p = .013). The intervention appeared to mitigate this "threshold effect"; number of problem behaviors did not predict risk of placement disruption in the treatment foster care group (p = .63). These findings replicate previous evidence linking child problem behavior to placement disruptions and further highlight the need for early preventative interventions.

  14. Is current disruption associated with an inverse cascade?

    Directory of Open Access Journals (Sweden)

    Z. Vörös

    2010-06-01

    Full Text Available Current disruption (CD and the related kinetic instabilities in the near-Earth magnetosphere represent physical mechanisms which can trigger multi-scale substorm activity including global reorganizations of the magnetosphere. Lui et al. (2008 proposed a CD scenario in which the kinetic scale linear modes grow and reach the typical dipolarization scales through an inverse cascade. The experimental verification of the inverse nonlinear cascade is based on wavelet analysis. In this paper the Hilbert-Huang transform is used which is suitable for nonlinear systems and allows to reconstruct the time-frequency representation of empirical decomposed modes in an adaptive manner. It was found that, in the Lui et al. (2008 event, the modes evolve globally from high-frequencies to low-frequencies. However, there are also local frequency evolution trends oriented towards high-frequencies, indicating that the underlying processes involve multi-scale physics and non-stationary fluctuations for which the simple inverse cascade scenario is not correct.

  15. Nicotine disrupts safety learning by enhancing fear associated with a safety cue via the dorsal hippocampus.

    Science.gov (United States)

    Connor, David A; Kutlu, Munir G; Gould, Thomas J

    2017-07-01

    Learned safety, a learning process in which a cue becomes associated with the absence of threat, is disrupted in individuals with post-traumatic stress disorder (PTSD). A bi-directional relationship exists between smoking and PTSD and one potential explanation is that nicotine-associated changes in cognition facilitate PTSD emotional dysregulation by disrupting safety associations. Therefore, we investigated whether nicotine would disrupt learned safety by enhancing fear associated with a safety cue. In the present study, C57BL/6 mice were administered acute or chronic nicotine and trained over three days in a differential backward trace conditioning paradigm consisting of five trials of a forward conditioned stimulus (CS)+ (Light) co-terminating with a footshock unconditioned stimulus followed by a backward CS- (Tone) presented 20 s after cessation of the unconditioned stimulus. Summation testing found that acute nicotine disrupted learned safety, but chronic nicotine had no effect. Another group of animals administered acute nicotine showed fear when presented with the backward CS (Light) alone, indicating the formation of a maladaptive fear association with the backward CS. Finally, we investigated the brain regions involved by administering nicotine directly into the dorsal hippocampus, ventral hippocampus, and prelimbic cortex. Infusion of nicotine into the dorsal hippocampus disrupted safety learning.

  16. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

    Science.gov (United States)

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-02-24

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

  17. Disruption of the neurexin 1 gene is associated with schizophrenia.

    NARCIS (Netherlands)

    Rujescu, D.; Ingason, A.; Cichon, S.; Pietilainen, O.P.H.; Barnes, M.R.; Toulopoulou, T.; Picchioni, M.; Vassos, E.; Ettinger, U.; Bramon, E.; Murray, R.; Ruggeri, M.; Tosato, S.; Bonetto, C.; Steinberg, S.; Sigurdsson, E.; Sigmundsson, T.; Petursson, H.; Gylfason, A; Olason, P.; Hardarsson, G.; Jonsdottir, G.A.; Gustafsson, O.; Fossdal, R.; Giegling, I.; Moller, H.J.; Hartmann, A.M.; Hoffmann, P.; Crombie, C.; Fraser, G.; Walker, N.; Lonnqvist, J.; Suvisaari, J.; Tuulio-Henriksson, A.; Djurovic, S.; Melle, I.; Andreassen, O.A.; Hansen, T.; Werge, T.; Kiemeney, L.A.L.M.; Franke, B.; Veltman, J.A.; Buizer-Voskamp, J.E.; Sabatti, C.; Ophoff, R.A.; Rietschel, M.; Nothen, Markus; Stefansson, K.; Peltonen, L.; St Clair, D.; Stefansson, H.; Collier, D.A.

    2009-01-01

    Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from

  18. Disruption of the neurexin 1 gene is associated with schizophrenia

    NARCIS (Netherlands)

    Rujescu, Dan; Ingason, Andres; Cichon, Sven; Pietilainen, Olli P. H.; Barnes, Michael R.; Toulopoulou, Timothea; Picchioni, Marco; Vassos, Evangelos; Ettinger, Ulrich; Bramon, Elvira; Murray, Robin; Ruggeri, Mirella; Tosato, Sarah; Bonetto, Chiara; Steinberg, Stacy; Sigurdsson, Engilbert; Sigmundsson, Thordur; Petursson, Hannes; Gylfason, Arnaldur; Olason, Pall I.; Hardarsson, Gudmundur; Jonsdottir, Gudrun A.; Gustafsson, Omar; Fossdal, Ragnheidur; Giegling, Ina; Moeller, Hans-Jurgen; Hartmann, Annette M.; Hoffmann, Per; Crombie, Caroline; Fraser, Gillian; Walker, Nicholas; Lonnqvist, Jouko; Suvisaari, Jaana; Tuulio-Henriksson, Annamari; Djurovic, Srdjan; Melle, Ingrid; Andreassen, Ole A.; Hansen, Thomas; Werge, Thomas; Kiemeney, Lambertus A.; Franke, Barbara; Veltman, Joris; Buizer-Voskamp, Jacobine E.; Sabatti, Chiara; Ophoff, Roel A.; Rietschel, Marcella; Noehen, Markus M.; Stefansson, Kari; Peltonen, Leena; St Clair, David

    2009-01-01

    Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from

  19. Disruption of the neurexin 1 gene is associated with schizophrenia

    DEFF Research Database (Denmark)

    Rujescu, Dan; Ingason, Andres; Cichon, Sven

    2009-01-01

    .15%) in controls. There was no common breakpoint and the CNVs varied from 18 to 420 kb. No CNVs were found in NRXN2 or NRXN3. We performed a Cochran-Mantel-Haenszel exact test to estimate association between all CNVs and schizophrenia (P = 0.13; OR = 1.73; 95% CI 0.81-3.50). Because the penetrance of NRXN1 CNVs...

  20. Tunneled dialysis catheter exchange with fibrin sheath disruption is not associated with increased rate of bacteremia.

    Science.gov (United States)

    Valliant, Amanda M; Chaudhry, Muhammad K; Yevzlin, Alexander S; Astor, Brad; Chan, Micah R

    2015-01-01

    Tunneled dialysis catheters are the most common form of vascular access among incident dialysis patients in the United States. Fibrin sheath formation is a frequent cause of late catheter dysfunction requiring an exchange procedure with balloon disruption of the fibrin sheath. It is unknown whether fibrin sheath disruption is associated with increased incidence of bacteremia or catheter failure. We reviewed all tunneled dialysis catheter exchange procedures at the University of Wisconsin between January 2008 and December 2011. The primary outcome was incidence of bacteremia, defined as positive blood cultures within 2 weeks of the procedure. Catheter failure, requiring intervention or replacement, was examined as a secondary outcome. Baseline characteristics examined included diabetic status, gender, race and age. A total of 163 procedures were reviewed; 67 (41.1%) had fibrin sheath disruption and 96 did not. Bacteremia occurred in 4.5% (3/67) of those with and 3.1% (3/97) of those without fibrin sheath disruption (p=0.65). Fibrin sheath disruption was not significantly associated with the risk of catheter failure (adjusted hazard ratio [aHR]=1.34; 95% confidence interval [CI]: 0.87-2.10; p=0.18). Diabetes was associated with greater risk of catheter failure (aHR=1.88; 95% CI: 1.19-2.95; p=0.006), whereas higher age was associated with a lower risk of catheter failure (aHR per 10 years=0.83; 95% CI: 0.72-0.96; p=0.01). This study demonstrates that there is no significant increase in bacteremia and subsequent catheter dysfunction rates after fibrin sheath disruption compared to simple over the wire exchange. These results are encouraging given the large numbers of patients utilizing tunneled catheters for initial hemodialysis access and the known rates of fibrin sheath formation leading to catheter failure.

  1. Obesity, Diabetes, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

    NARCIS (Netherlands)

    Legler, J.; Fletcher, T.; Govarts, E.; Porta, M.; Blumberg, B.; Heindel, J.J.; Trasande, L.

    2016-01-01

    Context: Obesityanddiabetes are epidemic in the European Union(EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. Objective: The objective was to estimate obesity, diabetes, and associated costs that can be

  2. Virus-associated activation of innate immunity induces rapid disruption of Peyer's patches in mice.

    Science.gov (United States)

    Heidegger, Simon; Anz, David; Stephan, Nicolas; Bohn, Bernadette; Herbst, Tina; Fendler, Wolfgang Peter; Suhartha, Nina; Sandholzer, Nadja; Kobold, Sebastian; Hotz, Christian; Eisenächer, Katharina; Radtke-Schuller, Susanne; Endres, Stefan; Bourquin, Carole

    2013-10-10

    Early in the course of infection, detection of pathogen-associated molecular patterns by innate immune receptors can shape the subsequent adaptive immune response. Here we investigate the influence of virus-associated innate immune activation on lymphocyte distribution in secondary lymphoid organs. We show for the first time that virus infection of mice induces rapid disruption of the Peyer's patches but not of other secondary lymphoid organs. The observed effect was not dependent on an active infectious process, but due to innate immune activation and could be mimicked by virus-associated molecular patterns such as the synthetic double-stranded RNA poly(I:C). Profound histomorphologic changes in Peyer's patches were associated with depletion of organ cellularity, most prominent among the B-cell subset. We demonstrate that the disruption is entirely dependent on type I interferon (IFN). At the cellular level, we show that virus-associated immune activation by IFN-α blocks B-cell trafficking to the Peyer's patches by downregulating expression of the homing molecule α4β7-integrin. In summary, our data identify a mechanism that results in type I IFN-dependent rapid but reversible disruption of intestinal lymphoid organs during systemic viral immune activation. We propose that such rerouted lymphocyte trafficking may impact the development of B-cell immunity to systemic viral pathogens.

  3. Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction

    Science.gov (United States)

    Xiao, Ping-Jie; Mitchell, Angela M.; Huang, Lu; Li, Chengwen; Samulski, R. Jude

    2016-01-01

    Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion. PMID:26942476

  4. Investigating the Association between Home-School Dissonance and Disruptive Classroom Behaviors for Urban Middle School Students

    Science.gov (United States)

    Tyler, Kenneth M.; Burris, Jennifer L.; Coleman, Sean T.

    2018-01-01

    Disruptive classroom behaviors are a major schooling dilemma in urban schools. While several contextual and motivational factors have been statistically associated with disruptive classroom behaviors, one overlooked factor has been home-school dissonance. The current study examined the relationship between 260 middle school students' reports of…

  5. Association between variations in the disrupted in schizophrenia 1 gene and schizophrenia: A meta-analysis.

    Science.gov (United States)

    Xu, Yiliang; Ren, Jun; Ye, Haihong

    2018-04-20

    Schizophrenia is a severe psychiatric disorder. Genetic and functional studies have strongly implicated the disrupted in schizophrenia 1 gene (DISC1) as a candidate susceptibility gene for schizophrenia. Moreover, recent association studies have indicated that several DISC1 single nucleotide polymorphisms (SNPs) are associated with schizophrenia. However, the association is hardly replicate in different ethnic group. Here, we performed a meta-analysis of the association between DISC1 SNPs and schizophrenia in which the samples were divided into subgroups according to ethnicity. Both rs3738401 and rs821616 showed not significantly association with schizophrenia in the Caucasian, Asian, Japanese or Han Chinese populations. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction

    International Nuclear Information System (INIS)

    Johnson-Lyles, Denise N.; Peifley, Kimberly; Lockett, Stephen; Neun, Barry W.; Hansen, Matthew; Clogston, Jeffrey; Stern, Stephan T.; McNeil, Scott E.

    2010-01-01

    Water soluble fullerenes, such as the hydroxylated fullerene, fullerenol (C 60 OH x ), are currently under development for diagnostic and therapeutic biomedical applications in the field of nanotechnology. These molecules have been shown to undergo urinary clearance, yet there is limited data available on their renal biocompatibility. Here we examine the biological responses of renal proximal tubule cells (LLC-PK1) exposed to fullerenol. Fullerenol was found to be cytotoxic in the millimolar range, with viability assessed by the sulforhodamine B and trypan blue assays. Fullerenol-induced cell death was associated with cytoskeleton disruption and autophagic vacuole accumulation. Interaction with the autophagy pathway was evaluated in vitro by Lysotracker Red dye uptake, LC3-II marker expression and TEM. Fullerenol treatment also resulted in coincident loss of cellular mitochondrial membrane potential and ATP depletion, as measured by the Mitotracker Red dye and the luciferin-luciferase assays, respectively. Fullerenol-induced ATP depletion and loss of mitochondrial potential were partially ameliorated by co-treatment with the autophagy inhibitor, 3-methyladenine. In vitro fullerenol treatment did not result in appreciable oxidative stress, as measured by lipid peroxide and glutathione content. Based on these data, it is hypothesized that cytoskeleton disruption may be an initiating event in fullerenol cytotoxicity, leading to subsequent autophagy dysfunction and loss of mitochondrial capacity. As nanoparticle-induced cytoskeleton disruption, autophagic vacuole accumulation and mitochondrial dysfunction are commonly reported in the literature, the proposed mechanism may be relevant for a variety of nanomaterials.

  7. Two microcephaly-associated novel missense mutations in CASK specifically disrupt the CASK-neurexin interaction.

    Science.gov (United States)

    LaConte, Leslie E W; Chavan, Vrushali; Elias, Abdallah F; Hudson, Cynthia; Schwanke, Corbin; Styren, Katie; Shoof, Jonathan; Kok, Fernando; Srivastava, Sarika; Mukherjee, Konark

    2018-03-01

    Deletion and truncation mutations in the X-linked gene CASK are associated with severe intellectual disability (ID), microcephaly and pontine and cerebellar hypoplasia in girls (MICPCH). The molecular origin of CASK-linked MICPCH is presumed to be due to disruption of the CASK-Tbr-1 interaction. This hypothesis, however, has not been directly tested. Missense variants in CASK are typically asymptomatic in girls. We report three severely affected girls with heterozygous CASK missense mutations (M519T (2), G659D (1)) who exhibit ID, microcephaly, and hindbrain hypoplasia. The mutation M519T results in the replacement of an evolutionarily invariant methionine located in the PDZ signaling domain known to be critical for the CASK-neurexin interaction. CASK M519T is incapable of binding to neurexin, suggesting a critically important role for the CASK-neurexin interaction. The mutation G659D is in the SH3 (Src homology 3) domain of CASK, replacing a semi-conserved glycine with aspartate. We demonstrate that the CASK G659D mutation affects the CASK protein in two independent ways: (1) it increases the protein's propensity to aggregate; and (2) it disrupts the interface between CASK's PDZ (PSD95, Dlg, ZO-1) and SH3 domains, inhibiting the CASK-neurexin interaction despite residing outside of the domain deemed critical for neurexin interaction. Since heterozygosity of other aggregation-inducing mutations (e.g., CASK W919R ) does not produce MICPCH, we suggest that the G659D mutation produces microcephaly by disrupting the CASK-neurexin interaction. Our results suggest that disruption of the CASK-neurexin interaction, not the CASK-Tbr-1 interaction, produces microcephaly and cerebellar hypoplasia. These findings underscore the importance of functional validation for variant classification.

  8. Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.

    Science.gov (United States)

    Young, Erica J; Aceti, Massimiliano; Griggs, Erica M; Fuchs, Rita A; Zigmond, Zachary; Rumbaugh, Gavin; Miller, Courtney A

    2014-01-15

    Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder. There is a growing consensus that memory is supported by structural and functional plasticity driven by F-actin polymerization in postsynaptic dendritic spines at excitatory synapses. However, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown. Conditioned place preference (n = 112) and context-induced reinstatement of self-administration (n = 19) were used to assess the role of F-actin polymerization and myosin II, a molecular motor that drives memory-promoting dendritic spine actin polymerization, in the maintenance of METH-associated memories and related structural plasticity. Memories formed through association with METH but not associations with foot shock or food reward were disrupted by a highly-specific actin cycling inhibitor when infused into the amygdala during the postconsolidation maintenance phase. This selective effect of depolymerization on METH-associated memory was immediate, persistent, and did not depend upon retrieval or strength of the association. Inhibition of non-muscle myosin II also resulted in a disruption of METH-associated memory. Thus, drug-associated memories seem to be actively maintained by a unique form of cycling F-actin driven by myosin II. This finding provides a potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory. The results further suggest that memory maintenance depends upon the preservation of polymerized actin. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. A residual granuloma in association with a dental implant.

    Science.gov (United States)

    McCracken, Michael S; Chavali, Ramakiran V; Al-Naief, Nasser Said; Eleazer, Paul D

    2012-04-01

    At times, dental implants are placed into sites with a history of periapical pathology. Sometimes the infection is active, and other times the tooth may have been extracted years before implant placement. In either case, the possibility exists for long-term residual cysts or infections that can negatively impact the prognosis of the implant. In this case report, an implant is placed into a healed mandibular ridge several months after extraction of the tooth. A radiolucency was noted on routine radiographic examination 2 years later. Surgical inspection and histology revealed a periapical granuloma with acute and chronic inflammatory cells. After surgical curettage of the site, the patient healed without complication. Implants may develop apical pathology as a result of a preexisting long-term residual infection.

  10. Milk quality parameters associated with the occurrence of veterinary drug residues in bulk tank milk

    Directory of Open Access Journals (Sweden)

    Lidia Cristina Almeida Picinin

    Full Text Available ABSTRACT Veterinary drug residues in bulk tank milk are important to all sectors of the dairy chain because they are one of the major factors which determine the safety of the final product. This study attempted to identify milk quality parameters that are associated with the occurrence of veterinary drug residues using multivariate principal component analysis (PCA. A total of 132 raw milk samples were collected from 45 dairy farms in the state of Minas Gerais - Brazil and analyzed for 42 analytes, including pyrethroids, macrocyclic lactones and antibacterials, using liquid chromatography coupled with mass spectrometry in tandem mode and gas chromatography with electron capture detection. Out of the 132 milk samples, 40 samples tested positive for at least one analyte (above the detection limit. The milk parameters associated with the antimicrobial residues by confirmatory tests were lactose and nonfat concentrations, as revealed by PCA. This analysis showed that fat and total solid concentrations, as well as the somatic cell and total bacteria counts were associated with macrocyclic lactone residues in bulk tank milk. A PCA assessing pyrethroid residues in bulk tank milk revealed that the lactose and nonfat solid concentrations and titratable acidity were inversely associated with these residues. Thus, the data analysis indicated that the veterinary drug residues were associated with certain milk quality parameters that can be used to target farms at higher risk of veterinary drug residue contamination for testing programs in combination with incentives, education and training programs to improve mammary health, milk hygiene and safety.

  11. Cannabidiol disrupts the reconsolidation of contextual drug-associated memories in Wistar rats.

    Science.gov (United States)

    de Carvalho, Cristiane Ribeiro; Takahashi, Reinaldo Naoto

    2017-05-01

    In addicts, craving and relapse are frequently induced by the recall of memories related to a drug experience. Several studies have demonstrated that drug-related memories are reactivated after exposure to environmental cues and may undergo reconsolidation, a process that can strengthen memories. Thus, reactivation of mnemonic traces provides an opportunity for disrupting memories that contribute to the pathological cycle of addiction. Here we used drug-induced conditioned place preference (CPP) to investigate whether cannabidiol (CBD), a phytocannabinoid, given just after reactivation sessions, would affect reconsolidation of drug-reward memory, reinstatement of morphine-CPP, or conditioned place aversion precipitated by naltrexone in Wistar rats. We found that CBD impaired the reconsolidation of preference for the environment previously paired with both morphine and cocaine. This disruption seems to be persistent, as the preference did not return after further reinstatement induced by priming drug and stress reinstatement. Moreover, in an established morphine-CPP, an injection of CBD after the exposure to a conditioning session led to a significant reduction of both morphine-CPP and subsequent conditioned place aversion precipitated by naltrexone in the same context. Thus, established memories induced by a drug of abuse can be blocked after reactivation of the drug experience. Taken together, these results provide evidence for the disruptive effect of CBD on reconsolidation of contextual drug-related memories and highlight its therapeutic potential to attenuate contextual memories associated with drugs of abuse and consequently to reduce the risk of relapse. © 2016 Society for the Study of Addiction.

  12. Residual stresses associated with welds in austenitic steel

    International Nuclear Information System (INIS)

    Fidler, R.

    1978-01-01

    Two exploratory welds have been made with AISI 316 austenitic steel and Armex GT electrodes by the manual metal-arc process, and residual stress measurements made in the as-welded condition and after various periods of stress relief. The results show that substantial stress relief occurs at temperatures of 850 0 and 750 0 C after 1 hr, but is not complete. The stress distributions are compared with those obtained from ferritic welds and the effect of differences in thermal expansion coefficients is examined using finite element analysis. (author)

  13. Association of serum levels of anti-myeloperoxidase antibody with retinal photoreceptor ellipsoid zone disruption in diabetic retinopathy.

    Science.gov (United States)

    Sinha, Shivani; Saxena, Sandeep; Prasad, Senthamizh; Mahdi, Abbas Ali; Bhasker, Shashi Kumar; Das, Siddharth; Krasnik, Vladimir; Caprnda, Martin; Opatrilova, Radka; Kruzliak, Peter

    2017-05-01

    To study the association of serum levels of anti-myeloperoxidase (MPO) antibody with retinal photoreceptor ellipsoid zone (EZ) disruption in diabetic retinopathy. Consecutive patients with type 2 DM [diabetes mellitus with no retinopathy (NODR; n=20); non-proliferative diabetic retinopathy (NPDR; n=18); proliferative diabetic retinopathy (PDR; n=16)] and healthy controls (n=20) between the ages of 40 and 65years were included. Disruption of EZ was graded by spectral domain optical coherence tomography as no disruption of EZ and disrupted EZ. The serum levels of anti-MPO antibody was analyzed using standard protocol. Association between the variables was evaluated using multiple regression analysis. A significant difference was found between the serum levels of anti-MPO antibody in various study groups (pdisruption and levels of anti-MPO antibody [adjusted odd's ratio (AOR)=1.079, CI 1.010-1.124, p=0.04]. A significant positive correlation was found between logMAR visual acuity and grade of disruption (AOR=1.008, CI 1.006-5.688, p=0.04). An increased serum anti-MPO antibody levels is associated with retinal photoreceptor EZ disruption and decreased visual acuity in diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Identification and disruption of bacteria associated with sheep scab mites-novel means of control?

    Science.gov (United States)

    Hall, S A; Mack, K; Blackwell, A; Evans, K A

    2015-10-01

    Psoroptes ovis mites, which cause psoroptic mange (sheep scab), were investigated to identify potential bacterial targets for endosymbiont control of sheep scab. In addition, transmission of bacteria to the sheep skin was investigated through the characterisation of bacteria present in P. ovis faecal trails and on the fleece environment by internal transcribed spacer (ITS) sequencing. A diverse range of bacteria was identified in addition to a potential endosymbiont candidate, Comamonas sp, which was detected in P. ovis by both ITS PCR and endosymbiont-specific PCR. Disruption of these bacteria within P. ovis, through the use of antibiotics, was explored; with significant reduction in mean mite survival when administered antibiotic diets compared with controls (LR4 = 23.12, P bacteria associated with P. ovis should be further investigated for novel control. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia.

    Science.gov (United States)

    Takei, Kunio; Yamasue, Hidenori; Abe, Osamu; Yamada, Haruyasu; Inoue, Hideyuki; Suga, Motomu; Sekita, Kayoko; Sasaki, Hiroki; Rogers, Mark; Aoki, Shigeki; Kasai, Kiyoto

    2008-08-01

    The fornix is a major projection of the hippocampus to and from other brain regions. A previous diffusion tensor imaging (DTI) study has reported disrupted integrity of the fornix in patients with schizophrenia. However, functional significance of the DTI abnormalities of the fornix in schizophrenia has not been fully studied yet. We investigated an association between DTI abnormalities of the fornix and impairment of memory organization in schizophrenia. Thirty-one patients with schizophrenia and 65 age- and gender-matched healthy controls underwent DTI, and fractional anisotropy (FA) and mean diffusivity (MD) were measured in cross-sections of fornix tractography. In addition, all of the patients and 32 controls performed a verbal learning task specialized for evaluating memory organization, the verbal memory subscale of the Wechsler Memory Scale-Revised, the category- and letter fluency tests, and the Japanese version of National Adult Reading Test. Statistically significant reduction of FA and increase of MD were found in the fornix of patients with schizophrenia compared with controls with no significant lateralization. A significant patients-specific correlation was found between increased MD in the left fornix and lower scores on utilization of semantic organization in the verbal learning task. In addition, increased MD in the right fornix showed a patients-specific association with poorer performance on the category fluency test, which indexes organization of long-term semantic memory. These patients-specific correlations, however, were not statistically lateralized to either hemisphere. These results indicate that disrupted integrity of the fornix contributes to impaired memory organization in schizophrenia.

  16. Disruption of Spectrin-Like Cytoskeleton in Differentiating Keratinocytes by PKCδ Activation Is Associated with Phosphorylated Adducin

    Science.gov (United States)

    Zhao, Kong-Nan; Masci, Paul P.; Lavin, Martin F.

    2011-01-01

    Spectrin is a central component of the cytoskeletal protein network in a variety of erythroid and non-erythroid cells. In keratinocytes, this protein has been shown to be pericytoplasmic and plasma membrane associated, but its characteristics and function have not been established in these cells. Here we demonstrate that spectrin increases dramatically in amount and is assembled into the cytoskeleton during differentiation in mouse and human keratinocytes. The spectrin-like cytoskeleton was predominantly organized in the granular and cornified layers of the epidermis and disrupted by actin filament inhibitors, but not by anti-mitotic drugs. When the cytoskeleton was disrupted PKCδ was activated by phosphorylation on Thr505. Specific inhibition of PKCδ(Thr505) activation with rottlerin prevented disruption of the spectrin-like cytoskeleton and the associated morphological changes that accompany differentiation. Rottlerin also inhibited specific phosphorylation of the PKCδ substrate adducin, a cytoskeletal protein. Furthermore, knock-down of endogenous adducin affected not only expression of adducin, but also spectrin and PKCδ, and severely disrupted organization of the spectrin-like cytoskeleton and cytoskeletal distribution of both adducin and PKCδ. These results demonstrate that organization of a spectrin-like cytoskeleton is associated with keratinocytes differentiation, and disruption of this cytoskeleton is mediated by either PKCδ(Thr505) phosphorylation associated with phosphorylated adducin or due to reduction of endogenous adducin, which normally connects and stabilizes the spectrin-actin complex. PMID:22163289

  17. Small bowel entrapment and ureteropelvic junction disruption associated with L3 Chance fracture-dislocation

    Science.gov (United States)

    Pesenti, Sebastien; Blondel, Benjamin; Faure, Alice; Peltier, Emilie; Launay, Franck; Jouve, Jean-Luc

    2016-01-01

    Paediatric Chance fracture are rare lesions but often associated with abdominal injuries. We herein present the case of a seven years old patient who sustained an entrapment of small bowel and an ureteropelvic disruption associated with a Chance fracture and spine dislocation following a traffic accident. Initial X-rays and computed tomographic (CT) scan showed a Chance fracture with dislocation of L3 vertebra, with an incarceration of a small bowel loop in the spinal canal and a complete section of the left lumbar ureter. Paraplegia was noticed on the initial neurological examination. A posterior L2-L4 osteosynthesis was performed firstly. In a second time she underwent a sus umbilical laparotomy to release the incarcerated jejunum loop in the spinal canal. An end-to-end anastomosis was performed on a JJ probe to suture the left injured ureter. One month after the traumatism, she started to complain of severe headaches related to a leakage of cerebrospinalis fluid. Three months after the traumatism there was a clear regression of the leakage. One year after the trauma, an anterior intervertebral fusion was done. At final follow-up, no neurologic recovery was noticed. In case of Chance fracture, all physicians should think about abdominal injuries even if the patient is asymptomatic. Initial abdominal CT scan and magnetic resonance imaging provide in such case crucial info for management of the spine and the associated lesions. PMID:27672641

  18. Nicotine Withdrawal Disrupts Contextual Learning but Not Recall of Prior Contextual Associations: Implications for Nicotine Addiction

    OpenAIRE

    Portugal, George S.; Gould, Thomas J.

    2008-01-01

    Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual...

  19. Associations of Intraoperative Flow Disruptions and or Teamwork during Robotic Assisted Radical Prostatectomy.

    Science.gov (United States)

    Weigl, Matthias; Weber, Jeannette; Hallett, Elyse; Pfandler, Michael; Schlenker, Boris; Becker, Armin; Catchpole, Ken

    2018-01-22

    To identify type and severity of surgical flow disruptions and to determine their impact on the perception of intraoperative teamwork. 40 radical prostatectomy cases were studied in an academic department for urology. A standardized observational tool for identification of type and severity of flow disruptions was applied during real-time prostatectomy procedures. Additionally, all OR team members evaluated intra-operative teamwork immediately after the procedure. Procedures were divided into four phases: pre-robot, docking, console time, and post-robot. A total of 2012 flow disruptions were observed with an average rate of 16.27 events per hour. The highest rate was during the robot docking phase. Although the frequency of disruption types varied across phases, the most severe disruptions were related to communication and coordination during the pre-robot and docking phase. Equipment- and communication-related disruptions were mostly severe during the time the surgeons were on the console. Among the surgeons, we identified a significant relationship between disruptions and intraoperative teamwork such that during procedures with frequent severe disruptions, surgeons experienced inferior teamwork (β = -.40, p=.01). This was not the case for nurses and anesthetists. Emphasis on improving OR team communication and coordination would help to establish efficient and smooth surgical workflow. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Widespread disruptive selection in the wild is associated with intense resource competition

    Science.gov (United States)

    2012-01-01

    Background Disruptive selection has been documented in a growing number of natural populations. Yet, its prevalence within individual systems remains unclear. Furthermore, few studies have sought to identify the ecological factors that promote disruptive selection in the wild. To address these issues, we surveyed 15 populations of Mexican spadefoot toad tadpoles, Spea multiplicata, and measured the prevalence of disruptive selection acting on resource-use phenotypes. We also evaluated the relationship between the strength of disruptive selection and the intensity of intraspecific competition—an ecological agent hypothesized to be an important driver of disruptive selection. Results Disruptive selection was the predominant mode of quadratic selection across all populations. However, a directional component of selection favoring an extreme ecomorph—a distinctive carnivore morph—was also common. Disruptive selection was strongest in populations experiencing the most intense intraspecific competition, whereas stabilizing selection was only found in populations experiencing relatively weak intraspecific competition. Conclusions Disruptive selection can be common in natural populations. Intraspecific competition for resources may be a key driver of such selection. PMID:22857143

  1. Disruptive tension under normalized atmospheric pulse and residual tension on lightning arresters power systems: statistical methods application. Practical results and comments; Ensaios de tensao disruptiva sob impulso atmosferico normalizado e tensao residual em para-raios para sistemas de potencia: a aplicacao de metodos estatisticos. Comentarios e resultados praticos

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, M.L.B. [ELETRONORTE, Brasilia (Brazil); Oliveira, A.L. [Eletricidade da Sao Paulo S.A. (ELETROPAULO), Sao Paulo, SP (Brazil)

    1991-12-31

    The necessity of complementary assays of disruptive tension under normalized atmospheric pulses and residual tension on lightning arresters, as well as the adequate use of a statistical treatment of its results are commented. Some statistical methods and its applicability on lightning arresters characteristics surveys, and its quality control are proposed 8 refs., 5 figs., 3 tabs.

  2. Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins.

    Science.gov (United States)

    Pradhan, Mohan R; Pal, Arumay; Hu, Zhongqiao; Kannan, Srinivasaraghavan; Chee Keong, Kwoh; Lane, David P; Verma, Chandra S

    2016-02-01

    Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using "Dehydrons." "Dehydrons" are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein-protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non-conserved dehydron-residues) from other interaction interfaces (conserved dehydron-residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation. © 2015 Wiley Periodicals, Inc.

  3. Association between Sleep Disruption and Levels of Lipids in Caucasians with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Wan Aizad Wan Mahmood

    2013-01-01

    Full Text Available Aim. To investigate the association between sleep quality and duration with lipid and glycaemic control in Caucasian subjects with type 2 diabetes. Methods. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI in 114 type 2 diabetes (T2DM subjects. Comparisons were made between subjects with different sleep quality and sleep duration. Hierarchical multiple regression analyses were used to determine contributors to metabolic parameters. Results. Subjects with poor sleep quality (PQ; PSQI ≥ 6 had higher systolic blood pressure, glycated haemoglobin, urine albumin : creatinine ratio (UAC, total cholesterol (TC, and triglycerides (TG ( for all compared to those with good sleep quality (GQ; PSQI ≤ 5. Long sleep duration (LSD subjects had higher TC and short sleep duration (SSD subjects had higher TG compared to those with medium sleep duration. Sleep duration and PSQI score were independent predictors of TC and low-density lipoprotein cholesterol (LDL, contributing to 14.0% and 6.1% of the total variance, respectively. Conclusions. In this Caucasian T2DM population, PQ is associated with adverse cardiovascular risk markers, and long and short sleep disruptions have an independent negative impact on lipids. Sleep assessment should be included as part of a diabetes clinic review.

  4. Depression and anxiety symptoms are associated to disruption of default mode network in subacute ischemic stroke.

    Science.gov (United States)

    Vicentini, Jéssica Elias; Weiler, Marina; Almeida, Sara Regina Meira; de Campos, Brunno Machado; Valler, Lenise; Li, Li Min

    2017-12-01

    Depression and anxiety symptoms are common after stroke and associated to reduction in quality of life and poor physical and social outcomes. The Default Mode Network (DMN) plays an important role in the emotional processing. We investigated whether these symptoms are associated to a disruption of DMN functional connectivity in the first month after stroke. Thirty-four subacute ischemic stroke patients were submitted to: 1) behavioral assessment through Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Structured Clinical Interview for DSM Disorders; 2) neuropsychological assessment using Mini Mental State Examination and Montreal Cognitive Assessment; 3) resting state functional magnetic resonance imaging acquisition using a 3 T scanner (Philips Achieva). Patients with depression and/or anxiety symptoms showed an increased DMN functional connectivity in left inferior parietal gyrus and left basal nuclei, when compared to stroke controls. Specific correlation between BDI/BAI scores and DMN functional connectivity indicated that depression symptoms are correlated with increased functional connectivity in left inferior parietal gyrus, while anxiety symptoms are correlated with increased functional connectivity in cerebellum, brainstem and right middle frontal gyrus. Our study provides new insights into the underlying mechanisms of post stroke depression and anxiety, suggesting an alternate explanation other than regional structural damage following ischemic event, that these psychiatric symptoms are related to brain network dysfunction.

  5. Association between Sleep Disruption and Levels of Lipids in Caucasians with Type 2 Diabetes.

    LENUS (Irish Health Repository)

    Wan Mahmood, Wan Aizad

    2013-08-29

    Aim. To investigate the association between sleep quality and duration with lipid and glycaemic control in Caucasian subjects with type 2 diabetes. Methods. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in 114 type 2 diabetes (T2DM) subjects. Comparisons were made between subjects with different sleep quality and sleep duration. Hierarchical multiple regression analyses were used to determine contributors to metabolic parameters. Results. Subjects with poor sleep quality (PQ; PSQI ≥ 6) had higher systolic blood pressure, glycated haemoglobin, urine albumin : creatinine ratio (UAC), total cholesterol (TC), and triglycerides (TG) (P < 0.05 for all) compared to those with good sleep quality (GQ; PSQI ≤ 5). Long sleep duration (LSD) subjects had higher TC and short sleep duration (SSD) subjects had higher TG compared to those with medium sleep duration. Sleep duration and PSQI score were independent predictors of TC and low-density lipoprotein cholesterol (LDL), contributing to 14.0% and 6.1% of the total variance, respectively. Conclusions. In this Caucasian T2DM population, PQ is associated with adverse cardiovascular risk markers, and long and short sleep disruptions have an independent negative impact on lipids. Sleep assessment should be included as part of a diabetes clinic review.

  6. Cold hands, warm feet: sleep deprivation disrupts thermoregulation and its association with vigilance.

    Science.gov (United States)

    Romeijn, Nico; Verweij, Ilse M; Koeleman, Anne; Mooij, Anne; Steimke, Rosa; Virkkala, Jussi; van der Werf, Ysbrand; Van Someren, Eus J W

    2012-12-01

    Vigilance is affected by induced and spontaneous skin temperature fluctuations. Whereas sleep deprivation strongly affects vigilance, no previous study examined in detail its effect on human skin temperature fluctuations and their association with vigilance. In a repeated-measures constant routine design, skin temperatures were assessed continuously from 14 locations while performance was assessed using a reaction time task, including eyes-open video monitoring, performed five times a day for 2 days, after a normal sleep or sleep deprivation night. Participants were seated in a dimly lit, temperature-controlled laboratory. Eight healthy young adults (five males, age 22.0 ± 1.8 yr (mean ± standard deviation)). One night of sleep deprivation. Mixed-effect regression models were used to evaluate the effect of sleep deprivation on skin temperature gradients of the upper (ear-mastoid), middle (hand-arm), and lower (foot-leg) body, and on the association between fluctuations in performance and in temperature gradients. Sleep deprivation induced a marked dissociation of thermoregulatory skin temperature gradients, indicative of attenuated heat loss from the hands co-occurring with enhanced heat loss from the feet. Sleep deprivation moreover attenuated the association between fluctuations in performance and temperature gradients; the association was best preserved for the upper body gradient. Sleep deprivation disrupts coordination of fluctuations in thermoregulatory skin temperature gradients. The dissociation of middle and lower body temperature gradients may therefore be evaluated as a marker for sleep debt, and the upper body gradient as a possible aid in vigilance assessment when sleep debt is unknown. Importantly, our findings suggest that sleep deprivation affects the coordination between skin blood flow fluctuations and the baroreceptor-mediated cardiovascular regulation that prevents venous pooling of blood in the lower limbs when there is the orthostatic

  7. Pesticide residues in grain from Kazakhstan and potential health risks associated with exposure to detected pesticides.

    Science.gov (United States)

    Lozowicka, B; Kaczynski, P; Paritova, Capital A Cyrillic Е; Kuzembekova, G B; Abzhalieva, A B; Sarsembayeva, N B; Alihan, K

    2014-02-01

    This paper presents the first study of pesticide residue results in grain from Kazakhstan. A total of 80 samples: barley, oat, rye, and wheat were collected and tested in the accredited laboratory. Among 180 pesticides, 10 active substances were detected. Banned pesticides, such as DDTs, γ-HCH, aldrin and diazinon were found in cereal grain. Chlorpyrifos methyl and pirimiphos methyl were the most frequently detected residues. No residues were found in 77.5% of the samples, 13.75% contained pesticide residues at or below MRLs, and 8.75% above MRLs. The greatest percentage of samples with residues (29%) was noted for wheat, and the lowest for rye (20%). Obtained data were used to estimate potential health risks associated with exposure to these pesticides. The highest estimated daily intakes (EDIs) were as follows: 789% of the ADI for aldrin (wheat) and 49.8% of the ADI for pirimiphos methyl (wheat and rye). The acute risk from aldrin and tebuconazole in wheat was 315.9% and 98.7% ARfD, respectively. The results show that despite the highest EDIs of pesticide residues in cereals, the current situation could not be considered a serious public health problem. Nevertheless, an investigation into continuous monitoring of pesticide residues in grain is recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Directory of Open Access Journals (Sweden)

    Irna Sufiawati

    Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  9. Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

    Directory of Open Access Journals (Sweden)

    Jana Husse

    Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

  10. Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder.

    Science.gov (United States)

    Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

    2017-01-01

    Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

    Science.gov (United States)

    Legler, Juliette; Fletcher, Tony; Govarts, Eva; Porta, Miquel; Blumberg, Bruce; Heindel, Jerrold J; Trasande, Leonardo

    2015-04-01

    Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555-5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6-86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200-56 400) with associated costs of €835 million (sensitivity analysis: €835 million-16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion. EDC exposures in the EU contribute

  12. Coxiella burnetii lipopolysaccharide blocks p38α-MAPK activation through the disruption of TLR-2 and TLR-4 association

    Directory of Open Access Journals (Sweden)

    Filippo eConti

    2015-01-01

    Full Text Available To survive in macrophages, Coxiella burnetii hijacks the activation pathway of macrophages. Recently, we have demonstrated that C. burnetii, via its lipopolysaccharide (LPS, avoids the activation of p38α-MAPK through an antagonistic engagement of Toll-like receptor (TLR-4. We investigated the fine-tuned mechanism leading to the absence of activation of the p38α-MAPK despite TLR-4 engagement. In macrophages challenged with Escherichia coli LPS or with the LPS from the avirulent variants of C. burnetii, TLR-4 and TLR-2 co-immunoprecipitated. This association was absent in cells challenged by the LPS of pathogenic C. burnetii. The disruption makes TLRs unable to signal during the recognition of the LPS of pathogenic C. burnetii. The disruption of TLR-2 and TLR-4 was induced by the re-organization of the macrophage cytoskeleton by C. burnetii LPS. Interestingly, blocking the actin cytoskeleton re-organization relieved the disruption of the association TLR-2/TLR-4 by pathogenic C. burnetii and rescued the p38α-MAPK activation by C. burnetii. We elucidated an unexpected mechanism allowing pathogenic C. burnetii to avoid activating macrophages by the disruption of the TLR-2 and TLR-4 association.

  13. Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Richter, Catherine A.; Martyniuk, Christopher J.; Annis, Mandy L.; Brumbaugh, William G.; Chasar, Lia C.; Denslow, Nancy D.; Tillitt, Donald E.

    2014-01-01

    Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates.

  14. Development of cassava plants and its mycorrhizal association in soil supplemented with sugarcane agroindustrial residue

    Directory of Open Access Journals (Sweden)

    Jorge Messias Leal Nascimento

    2014-02-01

    Full Text Available Application of organic agroindustrial residues on agriculture can be one way to improve the development and chemical composition of plants, reducing the cost with chemical fertilizers and impacts generated by the excessive use of them. Sugarcane agroindustrial residue has been generated in high quantity in Brazilian semiarid region and can be applied to cassava crop to improve its growth. The aim of this work was to evaluate the effect of application of sugarcane agroindustrial residue on the vegetative development, chemical composition and mycorrhizal association of cassava plants (Manihot esculenta var. Engana ladrão. It was performed an experiment in greenhouse with completely randomized design with four treatments of addition of sugarcane agroindustrial residue (0, 5, 10 and 15% with nine replicates. The addition of sugarcane agroindustrial residue increased fresh dry root biomass, leaf area, crude protein and mineral matter, without reducing the mycorrhizal colonization and glomerospores number. This type of residue can be one alternative to improve the nutritional value of these fodder.

  15. The BDGP gene disruption project: Single transposon insertions associated with 40 percent of Drosophila genes

    Energy Technology Data Exchange (ETDEWEB)

    Bellen, Hugo J.; Levis, Robert W.; Liao, Guochun; He, Yuchun; Carlson, Joseph W.; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P. Robin; Schulze, Karen L.; Rubin, Gerald M.; Hoskins, Roger A.; Spradling, Allan C.

    2004-01-13

    The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in more than 30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6,300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7,140 lines. It now includes individual lines predicted to disrupt 5,362 of the 13,666 currently annotated Drosophila genes (39 percent). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene mis-expression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool.

  16. A harsh parenting team? Maternal reports of coparenting and coercive parenting interact in association with children's disruptive behaviour.

    Science.gov (United States)

    Latham, Rachel M; Mark, Katharine M; Oliver, Bonamy R

    2017-05-01

    Parenting and coparenting are both important for children's adjustment, but their interaction has been little explored. Using a longitudinal design and considering two children per family, we investigated mothers' and fathers' perceptions of coparenting as moderators of associations between their coercive parenting and children's disruptive behaviour. Mothers and fathers from 106 'intact' families were included from the Twins, Family and Behaviour study. At Time 1 (M child age  = 3 years 11 months, SD child age  = 4.44 months) parents reported on their coercive parenting and children's disruptive behaviour via questionnaire; at Time 2 (M child age  = 4 years 8 months, SD child age  = 4.44 months) perceptions of coparenting and the marital relationship were collected by telephone interview. Questionnaire-based reports of children's disruptive behaviour were collected at follow-up (M child age  = 5 years 11 months, SD child age  = 5.52 months). Multilevel modelling was used to examine child-specific and family-wide effects. Conservative multilevel models including both maternal and paternal perceptions demonstrated that maternal perceptions of coparenting and overall coercive parenting interacted in their prediction of parent-reported child disruptive behaviour. Specifically, accounting for perceived marital quality, behavioural stability, and fathers' perceptions, only in the context of perceived higher quality coparenting was there a positive association between mother-reported overall coercive parenting and children's disruptive behaviour at follow-up. When combined with highly coercive parenting, maternal perceptions of high quality coparenting may be detrimental for children's adjustment. © 2016 Association for Child and Adolescent Mental Health.

  17. Atypical functional connectivity in autism spectrum disorder is associated with disrupted white matter microstructural organisation

    Directory of Open Access Journals (Sweden)

    Jane eMcGrath

    2013-09-01

    Full Text Available Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were 1. to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM in ASD and 2. to examine the relationships between aberrant neural connectivity and behaviour in ASD. 22 individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19 and five paired regions: left caudate head, left caudate body, left uncus, left thalamus and left cuneus. Measures of WM microstructural organisation were extracted from these tracts. Fractional anisotropy reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant white matter microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute 1. to abnormal functional connectivity and 2. to atypical visuospatial processing in ASD.

  18. The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development

    Energy Technology Data Exchange (ETDEWEB)

    Veldhoen, Nik [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada); Skirrow, Rachel C. [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Osachoff, Heather [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Wigmore, Heidi [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Clapson, David J. [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada); Gunderson, Mark P. [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada); Van Aggelen, Graham [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Helbing, Caren C. [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada)]. E-mail: chelbing@uvic.ca

    2006-12-01

    We investigated whether exposure to environmentally relevant concentrations of the bactericidal agent, triclosan, induces changes in the thyroid hormone-mediated process of metamorphosis of the North American bullfrog, Rana catesbeiana and alters the expression profile of thyroid hormone receptor (TR) {alpha} and {beta}, basic transcription element binding protein (BTEB) and proliferating nuclear cell antigen (PCNA) gene transcripts. Premetamorphic tadpoles were immersed in environmentally relevant concentrations of triclosan and injected with 1 x 10{sup -11} mol/g body weight 3,5,3'-triiodothyronine (T{sub 3}) or vehicle control. Morphometric measurements and steady-state mRNA levels obtained by quantitative polymerase chain reaction were determined. mRNA abundance was also examined in Xenopus laevis XTC-2 cells treated with triclosan and/or 10 nM T{sub 3}. Tadpoles pretreated with triclosan concentrations as low as 0.15 {+-} 0.03 {mu}g/L for 4 days showed increased hindlimb development and a decrease in total body weight following T{sub 3} administration. Triclosan exposure also resulted in decreased T{sub 3}-mediated TR{beta} mRNA expression in the tadpole tail fin and increased levels of PCNA transcript in the brain within 48 h of T{sub 3} treatment whereas TR{alpha} and BTEB were unaffected. Triclosan alone altered thyroid hormone receptor {alpha} transcript levels in the brain of premetamorphic tadpoles and induced a transient weight loss. In XTC-2 cells, exposure to T{sub 3} plus nominal concentrations of triclosan as low as 0.03 {mu}g/L for 24 h resulted in altered thyroid hormone receptor mRNA expression. Exposure to low levels of triclosan disrupts thyroid hormone-associated gene expression and can alter the rate of thyroid hormone-mediated postembryonic anuran development.

  19. Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward-associated memory in rats.

    Science.gov (United States)

    Fang, Qin; Li, Fang-Qiong; Li, Yan-Qin; Xue, Yan-Xue; He, Ying-Ying; Liu, Jian-Feng; Lu, Lin; Wang, Ji-Shi

    2011-10-01

    Exposure to cues previously associated with drug intake leads to relapse by activating previously acquired memories. Based on previous findings, in which cannabinoid CB(1) receptors were found to be critically involved in specific aspects of learning and memory, we investigated the role of CB(1) receptors in nicotine reward memory using a rat conditioned place preference (CPP) model. In Experiment 1, rats were trained for CPP with alternating injections of nicotine (0.5mg/kg, s.c.) and saline to acquire the nicotine-conditioned memory. To examine the effects of rimonabant on the reconsolidation of nicotine reward memory, rats were administered rimonabant (0, 0.3, and 3.0mg/kg, i.p.) immediately after reexposure to the drug-paired context. In Experiment 2, rats were trained for CPP similarly to Experiment 1. To examine the effects of rimonabant on the reinstatement of nicotine reward memory, rimonabant (0, 0.3, and 3.0mg/kg, i.p.) was administered before the test of nicotine-induced CPP reinstatement. In Experiment 3, to evaluate whether rimonabant itself produces a reward memory, rats were trained for CPP with alternating injections of different doses of rimonabant (0, 0.3, and 3.0mg/kg) and saline. Rimonabant at a dose of 3.0mg/kg significantly disrupted the reconsolidation of nicotine memory and significantly blocked the reinstatement of nicotine-induced CPP. However, rimonabant itself did not produce CPP. These findings provide clear evidence that CB(1) receptors play a role in nicotine reward memory, suggesting that CB(1) receptor antagonists may be a potential target for managing nicotine addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development

    International Nuclear Information System (INIS)

    Veldhoen, Nik; Skirrow, Rachel C.; Osachoff, Heather; Wigmore, Heidi; Clapson, David J.; Gunderson, Mark P.; Van Aggelen, Graham; Helbing, Caren C.

    2006-01-01

    We investigated whether exposure to environmentally relevant concentrations of the bactericidal agent, triclosan, induces changes in the thyroid hormone-mediated process of metamorphosis of the North American bullfrog, Rana catesbeiana and alters the expression profile of thyroid hormone receptor (TR) α and β, basic transcription element binding protein (BTEB) and proliferating nuclear cell antigen (PCNA) gene transcripts. Premetamorphic tadpoles were immersed in environmentally relevant concentrations of triclosan and injected with 1 x 10 -11 mol/g body weight 3,5,3'-triiodothyronine (T 3 ) or vehicle control. Morphometric measurements and steady-state mRNA levels obtained by quantitative polymerase chain reaction were determined. mRNA abundance was also examined in Xenopus laevis XTC-2 cells treated with triclosan and/or 10 nM T 3 . Tadpoles pretreated with triclosan concentrations as low as 0.15 ± 0.03 μg/L for 4 days showed increased hindlimb development and a decrease in total body weight following T 3 administration. Triclosan exposure also resulted in decreased T 3 -mediated TRβ mRNA expression in the tadpole tail fin and increased levels of PCNA transcript in the brain within 48 h of T 3 treatment whereas TRα and BTEB were unaffected. Triclosan alone altered thyroid hormone receptor α transcript levels in the brain of premetamorphic tadpoles and induced a transient weight loss. In XTC-2 cells, exposure to T 3 plus nominal concentrations of triclosan as low as 0.03 μg/L for 24 h resulted in altered thyroid hormone receptor mRNA expression. Exposure to low levels of triclosan disrupts thyroid hormone-associated gene expression and can alter the rate of thyroid hormone-mediated postembryonic anuran development

  1. Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat.

    Directory of Open Access Journals (Sweden)

    Mitsunori Miyazaki

    Full Text Available It is well known that spontaneously hypertensive rats (SHR develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007 linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including Mck, Ttn and Mef2c. We next performed circadian time-course collections at a young age (8 weeks; pre-hypertensive and adult age (22 weeks; hypertensive to determine if clock gene expression was disrupted in gastrocnemius, heart and liver tissues prior to or after the rats became hypertensive. We found that hypertensive/hypertrophic SHR showed a dampening of peak Bmal1 and Rev-erb expression in the liver, and the clock-controlled gene Pgc1α in the gastrocnemius. In addition, the core-clock gene Clock and the muscle-specific, clock-controlled gene Myod1, no longer maintained a circadian pattern of expression in gastrocnemius from the hypertensive SHR. These findings provide a framework to suggest a mechanism whereby chronic heart failure leads to skeletal muscle pathologies; prolonged dysregulation of the molecular clock in skeletal muscle results in altered Clock, Pgc1α and Myod1 expression which in turn leads to the mis-regulation of target genes important for mechanical and metabolic function of skeletal muscle.

  2. Literature mining of protein-residue associations with graph rules learned through distant supervision

    Directory of Open Access Journals (Sweden)

    Ravikumar KE

    2012-10-01

    Full Text Available Abstract Background We propose a method for automatic extraction of protein-specific residue mentions from the biomedical literature. The method searches text for mentions of amino acids at specific sequence positions and attempts to correctly associate each mention with a protein also named in the text. The methods presented in this work will enable improved protein functional site extraction from articles, ultimately supporting protein function prediction. Our method made use of linguistic patterns for identifying the amino acid residue mentions in text. Further, we applied an automated graph-based method to learn syntactic patterns corresponding to protein-residue pairs mentioned in the text. We finally present an approach to automated construction of relevant training and test data using the distant supervision model. Results The performance of the method was assessed by extracting protein-residue relations from a new automatically generated test set of sentences containing high confidence examples found using distant supervision. It achieved a F-measure of 0.84 on automatically created silver corpus and 0.79 on a manually annotated gold data set for this task, outperforming previous methods. Conclusions The primary contributions of this work are to (1 demonstrate the effectiveness of distant supervision for automatic creation of training data for protein-residue relation extraction, substantially reducing the effort and time involved in manual annotation of a data set and (2 show that the graph-based relation extraction approach we used generalizes well to the problem of protein-residue association extraction. This work paves the way towards effective extraction of protein functional residues from the literature.

  3. Literature mining of protein-residue associations with graph rules learned through distant supervision.

    Science.gov (United States)

    Ravikumar, Ke; Liu, Haibin; Cohn, Judith D; Wall, Michael E; Verspoor, Karin

    2012-10-05

    We propose a method for automatic extraction of protein-specific residue mentions from the biomedical literature. The method searches text for mentions of amino acids at specific sequence positions and attempts to correctly associate each mention with a protein also named in the text. The methods presented in this work will enable improved protein functional site extraction from articles, ultimately supporting protein function prediction. Our method made use of linguistic patterns for identifying the amino acid residue mentions in text. Further, we applied an automated graph-based method to learn syntactic patterns corresponding to protein-residue pairs mentioned in the text. We finally present an approach to automated construction of relevant training and test data using the distant supervision model. The performance of the method was assessed by extracting protein-residue relations from a new automatically generated test set of sentences containing high confidence examples found using distant supervision. It achieved a F-measure of 0.84 on automatically created silver corpus and 0.79 on a manually annotated gold data set for this task, outperforming previous methods. The primary contributions of this work are to (1) demonstrate the effectiveness of distant supervision for automatic creation of training data for protein-residue relation extraction, substantially reducing the effort and time involved in manual annotation of a data set and (2) show that the graph-based relation extraction approach we used generalizes well to the problem of protein-residue association extraction. This work paves the way towards effective extraction of protein functional residues from the literature.

  4. Studies on representative disruption scenarios, associated electromagnetic and heat loads and operation window in ITER

    International Nuclear Information System (INIS)

    Fujieda, Hirobumi; Shimada, Michiya; Kawano, Yasunori; Ohmori, Junji; Neyatani, Yuzuru; Sugihara, Masayoshi; Gribov, Yuri; Ioki, Kimihiro; Khayrutdinov, Rustan; Lukash, Victor

    2007-07-01

    The impacts of plasma disruptions on ITER have been investigated in detail to confirm the robustness of the design of the machine to the potential consequential loads. The loads include both electromagnetic (EM) and heat loads on the in-vessel components and the vacuum vessel (VV). Several representative disruption scenarios are specified based on newly derived physics guidelines for the shortest current quench time as well as the maximum product of halo current fraction and toroidal peaking factor arising from disruptions in ITER. Disruption simulations with the DINA code and EM load analyses with a 3D finite element method (FEM) code are performed for these scenarios. Some margins are confirmed in the EM load on in-vessel components due to induced eddy and halo currents for these representative scenarios. However, the margins are not very large. The heat load on various parts of the first wall due to the vertical movement and the thermal quench (TQ) is calculated with a 2D heat conduction code based on the database of heat deposition during disruptions and simulation results with the DINA code. It is found that the beryllium (Be) wall will not melt during the vertical movement. Significant melting is anticipated for the upper Be wall and tungsten divertor baffle due to the TQ after the vertical movement. However, its impact could be substantially mitigated by implementing a reliable detection system of the vertical movement and a mitigation system, e.g., massive noble gas injection (MGI). Some melting of the upper Be wall is anticipated at major disruptions (MD). At least several tens of unmitigated disruptions must be considered even if an advanced prediction/mitigation system is implemented. With these unmitigated disruptions, the loss of Be layer is expected to be within approx. = 30-100 μm/event out of 10 mm thick Be first wall. Various post processing programs of the results simulated with the DINA code, which are developed for the design work, are

  5. An Auto-Associative Residual Processing and K-means Clustering Approach for Anemometer Health Assessment

    Directory of Open Access Journals (Sweden)

    David Siegel

    2011-01-01

    Full Text Available This paper presents a health assessment methodology, as well as specific residual processing and figure of merit algorithms for anemometers in two different configurations. The methodology and algorithms are applied to data sets provided by the Prognostics and Health Management Society 2011 Data Challenge. The two configurations consist of the “paired” data set in which two anemometers are positioned at the same height, and the “shear” data set which includes an array of anemometers at different heights. Various wind speed statistics, wind direction, and ambient temperature information are provided, in which the objective is to classify the anemometer health status during a set of samples from a 5 day period. The proposed health assessment methodology consists of a set of data processing steps that include: data filtering and pre-processing, a residual or difference calculation, and a k-means clustering based figure of merit calculation. The residual processing for the paired data set was performed using a straightforward difference calculation, while the shear data set utilized an additional set of algorithm processing steps to calculate a weighted residual value for each anemometer. The residual processing algorithm for the shear data set used a set of auto-associative neural network models to learn the underlying correlation relationship between the anemometer sensors and to calculate a weighted residual value for each of the anemometer wind speed measurements. A figure of merit value based on the mean value of the smaller of the two clusters for the wind speed residual is used to determine the health status of each anemometer. Overall, the proposed methodology and algorithms show promise, in that the results from this approach resulted in the top score for the PHM 2011 Data Challenge Competition. Using different clustering algorithms or density estimation methods for the figure of merit calculation is being considered for future work.

  6. An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed

    OpenAIRE

    Forman, Oliver P.; Hitti, Rebekkah J.; Pettitt, Louise; Jenkins, Christopher A.; O?Brien, Dennis P.; Shelton, G. Diane; De Risio, Luisa; Quintana, Rodrigo Gutierrez; Beltran, Elsa; Mellersh, Cathryn

    2016-01-01

    Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genot...

  7. The Association Between Insomnia-related Sleep Disruptions and Cognitive Dysfunction during the Inter-episode Phase of Bipolar Disorder

    OpenAIRE

    Kanady, Jennifer Christine

    2015-01-01

    Sleep disturbance and cognitive dysfunction are two key domains of impairment during the inter-episode phase of bipolar disorder. Despite considerable evidence demonstrating the importance of sleep for cognition in healthy and sleep-disordered samples, this link has been minimally examined in bipolar disorder. Thus, the present study tested the association between insomnia-related sleep disruptions and cognitive functioning during inter-episode bipolar disorder. Forty-seven participants with ...

  8. Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer's disease.

    Science.gov (United States)

    Firbank, Michael J; Blamire, Andrew M; Krishnan, Mani S; Teodorczuk, Andrew; English, Philip; Gholkar, Anil; Harrison, Roger; O'Brien, John T

    2007-05-15

    Hippocampal atrophy and posterior cingulate hypometabolism are common features of both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). These regions show correlated activity at rest as part of the 'default network', and they are connected by the cingulum, a white matter (WM) tract. We hypothesised that hippocampal atrophy would be associated with disruption of the cingulum, as determined by diffusion tensor imaging. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with a T1 weighted 3D sequence and diffusion tensor FLAIR imaging. The T1 images were segmented into grey and white matter and spatially normalised using SPM. Hippocampal atrophy was estimated by calculating the mean grey matter (GM) volume from a region of interest in standard space and global atrophy from the total CSF segmentation. Fractional anisotropy (FA) maps were calculated and also spatially normalised. Using SPM, a multivariate correlation of FA against hippocampal GM, global atrophy and disease group was performed. We found a bilateral region adjacent to the posterior cingulate and encompassing a branch of the cingulum where global atrophy correlated with fractional anisotropy, after controlling for diagnosis and hippocampal GM. The results suggest that dementia disease progression as measured by global atrophy is associated with disruption of the white matter which connects posterior cingulate and lateral parietal regions. Hence, in addition to the hypometabolism in these regions in AD and DLB, there is also disruption to the white matter connecting them. Future studies are needed to determine whether the disruption precedes or is consequent on atrophy or hypometabolism.

  9. Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans.

    Science.gov (United States)

    Tubbs, Emily; Chanon, Stéphanie; Robert, Maud; Bendridi, Nadia; Bidaux, Gabriel; Chauvin, Marie-Agnès; Ji-Cao, Jingwei; Durand, Christine; Gauvrit-Ramette, Daphné; Vidal, Hubert; Lefai, Etienne; Rieusset, Jennifer

    2018-04-01

    Modifications of the interactions between endoplasmic reticulum (ER) and mitochondria, defined as mitochondria-associated membranes (MAMs), were recently shown to be involved in the control of hepatic insulin action and glucose homeostasis, but with conflicting results. Whereas skeletal muscle is the primary site of insulin-mediated glucose uptake and the main target for alterations in insulin-resistant states, the relevance of MAM integrity in muscle insulin resistance is unknown. Deciphering the importance of MAMs on muscle insulin signaling could help to clarify this controversy. Here, we show in skeletal muscle of different mice models of obesity and type 2 diabetes (T2D) a marked disruption of ER-mitochondria interactions as an early event preceding mitochondrial dysfunction and insulin resistance. Furthermore, in human myotubes, palmitate-induced insulin resistance is associated with a reduction of structural and functional ER-mitochondria interactions. Importantly, experimental increase of ER-mitochondria contacts in human myotubes prevents palmitate-induced alterations of insulin signaling and action, whereas disruption of MAM integrity alters the action of the hormone. Lastly, we found an association between altered insulin signaling and ER-mitochondria interactions in human myotubes from obese subjects with or without T2D compared with healthy lean subjects. Collectively, our data reveal a new role of MAM integrity in insulin action of skeletal muscle and highlight MAM disruption as an essential subcellular alteration associated with muscle insulin resistance in mice and humans. Therefore, reduced ER-mitochondria coupling could be a common alteration of several insulin-sensitive tissues playing a key role in altered glucose homeostasis in the context of obesity and T2D. © 2018 by the American Diabetes Association.

  10. Atypical language laterality is associated with large-scale disruption of network integration in children with intractable focal epilepsy.

    Science.gov (United States)

    Ibrahim, George M; Morgan, Benjamin R; Doesburg, Sam M; Taylor, Margot J; Pang, Elizabeth W; Donner, Elizabeth; Go, Cristina Y; Rutka, James T; Snead, O Carter

    2015-04-01

    Epilepsy is associated with disruption of integration in distributed networks, together with altered localization for functions such as expressive language. The relation between atypical network connectivity and altered localization is unknown. In the current study we tested whether atypical expressive language laterality was associated with the alteration of large-scale network integration in children with medically-intractable localization-related epilepsy (LRE). Twenty-three right-handed children (age range 8-17) with medically-intractable LRE performed a verb generation task in fMRI. Language network activation was identified and the Laterality index (LI) was calculated within the pars triangularis and pars opercularis. Resting-state data from the same cohort were subjected to independent component analysis. Dual regression was used to identify associations between resting-state integration and LI values. Higher positive values of the LI, indicating typical language localization were associated with stronger functional integration of various networks including the default mode network (DMN). The normally symmetric resting-state networks showed a pattern of lateralized connectivity mirroring that of language function. The association between atypical language localization and network integration implies a widespread disruption of neural network development. These findings may inform the interpretation of localization studies by providing novel insights into reorganization of neural networks in epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Association of regional gray matter volumes in the brain with disruptive behavior disorders in male and female children.

    Science.gov (United States)

    Michalska, Kalina J; Decety, Jean; Zeffiro, Thomas A; Lahey, Benjamin B

    2015-01-01

    Because the disruptive behavior disorders are highly impairing conditions, it is important to determine if structural variations in brain are associated early in life with these problems among children. Structural MRI data were acquired from 111 9-11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for oppositional defiant disorder and/or conduct disorder and 68 healthy controls. Voxel-based morphometry was used to examine associations of behavioral measures with gray matter volumes in whole-brain analyses. Unlike previous studies, variation in gray matter volume was not found to be associated with a disruptive behavior disorder diagnosis in any brain region at p < .05 with FWE correction. Nonetheless, an inverse nonlinear association of the number of conduct disorder (CD) symptoms with gray matter volume along the left superior temporal sulcus was significant in the full sample (p < .05 with FWE correction), with a trend in the right hemisphere (p < 0.001 uncorrected). There also was a trend toward a stronger association of the number of CD symptoms with gray matter volume along the left superior temporal sulcus in girls than boys. The present findings did not replicate previous findings of reduced gray matter volumes in the anterior insula, amygdala, and frontal cortex in youth with CD, but are consistent with previous findings of reduced gray matter volumes in temporal regions, particularly in girls.

  12. Cross-hemispheric Alternating Current Stimulation During a Nap Disrupts Slow Wave Activity and Associated Memory Consolidation.

    Science.gov (United States)

    Garside, Peter; Arizpe, Joseph; Lau, Chi-Ieong; Goh, Crystal; Walsh, Vincent

    2015-01-01

    Slow Wave Activity (SWA), the low frequency (nap however. We applied transcranial alternating current stimulation (tACS) - which, with a cross-hemispheric electrode montage (F3 and F4 - International 10:20 EEG system), is able to disrupt brain oscillations-to determine if disruption of low frequency oscillation generation during afternoon nap is causally related to disruption in declarative memory consolidation. Eight human subjects each participated in stimulation and sham nap sessions. A verbal paired associate learning (PAL) task measured memory changes. During each nap period, five 5-min stimulation (0.75 Hz cross-hemispheric frontal tACS) or sham intervals were applied with 1-min post-stimulation intervals (PSI's). Spectral EEG power for Slow (0.7-0.8 Hz), Delta (1.0-4.0 Hz), Theta (4.0-8.0 Hz), Alpha (8.0-12.0 Hz), and Spindle-range (12.0-14.0) frequencies was analyzed during the 1-min preceding the onset of stimulation and the 1-min PSI's. As hypothesized, power reduction due to stimulation positively correlated with reduction in word-pair recall post-nap specifically for Slow (P nap. Published by Elsevier Inc.

  13. Sleep disruption and duration in late pregnancy is associated with excess gestational weight gain among overweight and obese women.

    Science.gov (United States)

    Gay, Caryl L; Richoux, Sarah E; Beebe, Kathleen R; Lee, Kathryn A

    2017-06-01

    Poor sleep during pregnancy has been associated with poorer birth outcomes. High body mass index (BMI) is often associated with poor sleep, but little is known about the relationship between gestational weight gain and sleep in late pregnancy. The purpose of this study was to evaluate the relationships of both gestational weight gain and pre-pregnancy BMI to objective and subjective measures of sleep during late pregnancy. Pregnant women (n=128) were recruited from prenatal clinics and childbirth classes primarily serving low-income women. Their sleep (disruption and duration) was objectively assessed in their last month of pregnancy with 72 hours of wrist actigraphy monitoring. Their perceived sleep quality was assessed with the Pittsburgh Sleep Quality Index. Pre-pregnancy and late pregnancy height and weight were assessed by self-report and used to calculate BMI and gestational weight gain, which were then grouped into standardized categories. Mean Pittsburgh Sleep Quality Index score was 6.8 ± 3.1 (range 2-16). Sixty percent had excess gestational weight gain and it was associated with poorer perceived sleep quality, but was unrelated to objective measures of sleep duration and disruption. Pre-pregnancy BMI was unrelated to all sleep parameters. However, analyses of the interaction of pre-pregnancy BMI and gestational weight gain indicated that excess weight gain was associated with shorter sleep duration and more sleep disruption, but only among women who were overweight before pregnancy. Pregnancy is an opportunity to promote long-term women's health with a better understanding of the relationship between weight management and healthy sleep habits. © 2017 Wiley Periodicals, Inc.

  14. Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption.

    Science.gov (United States)

    Touitou, Yvan; Reinberg, Alain; Touitou, David

    2017-03-15

    Exposure to Artificial Light At Night (ALAN) results in a disruption of the circadian system, which is deleterious to health. In industrialized countries, 75% of the total workforce is estimated to have been involved in shift work and night work. Epidemiologic studies, mainly of nurses, have revealed an association between sustained night work and a 50-100% higher incidence of breast cancer. The potential and multifactorial mechanisms of the effects include the suppression of melatonin secretion by ALAN, sleep deprivation, and circadian disruption. Shift and/or night work generally decreases the time spent sleeping, and it disrupts the circadian time structure. In the long run, this desynchronization is detrimental to health, as underscored by a large number of epidemiological studies that have uncovered elevated rates of several diseases, including cancer, diabetes, cardiovascular risks, obesity, mood disorders and age-related macular degeneration. It amounts to a public health issue in the light of the very substantial number of individuals involved. The IARC has classified shift work in group 2A of "probable carcinogens to humans" since "they involve a circadian disorganization". Countermeasures to the effects of ALAN, such as melatonin, bright light, or psychotropic drugs, have been proposed as a means to combat circadian clock disruption and improve adaptation to shift and night work. We review the evidence for the ALAN impacts on health. Furthermore, we highlight the importance of an in-depth mechanistic understanding to combat the detrimental properties of exposure to ALAN and develop strategies of prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Quality of life development during initial hemodialysis therapy and association with loss of residual renal function

    DEFF Research Database (Denmark)

    Poulsen, Christina G; Kjaergaard, Krista D; Peters, Christian D

    2017-01-01

    , especially diabetes, hospital admissions, female gender, and age were strongly associated with lower HRQOL in cross sectional analysis. DISCUSSION: Preservation of residual renal function seems to be important for HRQOL. In newly started HD patients, HRQOL showed little change after 12 months. HRQOL...... was negatively affected by comorbidity, especially diabetes, hospital admissions, female gender, and age.......INTRODUCTION: Health related quality of life (HRQOL) is markedly reduced in hemodialysis patients compared to the general population. We investigated the course of self-reported HRQOL over time and the association with selected factors, focusing on changes in glomerular filtration rate (GFR...

  16. Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

    Science.gov (United States)

    Tugizov, Sharof

    2016-01-01

    Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

  17. Drawing a Transductive Ecosophy in Process: Technological Arts, Residual Matter, Associated Milieus

    Directory of Open Access Journals (Sweden)

    Gisèle Trudel

    2015-06-01

    Full Text Available Drawing a Transductive Ecosophy in Process: Technological Arts, Residual Matter, Associated Milieus by Gisèle Trudel. NANO: New American Notes Online, Issue 7: The Aesthetics of Trash - nanocrit.com. This text examines the tetralogy of media artworks about residual matter produced by Ælab between 2008 and 2014. Taking its own title as a diagram (Deleuze and Guattari Mille Plateaux, it charts and builds on the processes of these artworks, elucidating their relations to materiality, philosophy and technicity. Technological research-creation becomes in these instances a transdisciplinary aesthetic act, emerging from an ecology of practices that combine humans, non-humans and waste matter in an effort to increase attentiveness in actions.

  18. The Association between Nutritional Markers and Biochemical Parameters and Residual Renal Function in Peritoneal Dialysis Patients.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Residual renal function (RRF is an important prognostic factor for peritoneal dialysis patients as it influences the quality of life and mortality. This study was conducted to explore the potential factors correlated with RRF. A cross-sectional study was conducted by recruiting 155 patients with residual GFR more than 1mL/min per 1.73m2 at the initiation of peritoneal dialysis. We collected the demographic characteristics, nutritional markers and biochemical parameters of all participants, and analyzed the correlation between these variables and residual GFR as well. The odds ratio of RRF loss associated with each of the nutritional markers and biochemical parameters were estimated by logistic regression model. The residual GFR was negatively correlated with serum phosphate (ORQ3 = 2.67, 95%CI: 1.03-6.92; ORQ4 = 3.45, 95%CI: 1.35-9.04, magnesium (ORQ4 = 3.77, 95%CI: 1.48-3.63, and creatinine (ORQ3 = 2.93, 95%CI: 1.09-7.88; ORQ4 = 8.64 95%CI: 2.79-26.78, while positively associated with normalized protein catabolic rate (ORQ3 = 0.24, 95%CI: 0.09-0.65; ORQ4 = 0.11, 95%CI: 0.03-0.35, 24 hours urine volume(ORQ1 = 22.87, 95%CI: 2.76-189.24; ORQ3 = 0.08, 95%CI: 0.02-0.28 and serum chlorine concentrations (ORQ1 = 5.34, 95%CI: 1.94-14.68; ORQ4 = 0.28, 95%CI: 0.09-0.85, respectively. Our study suggested that the nutritional markers and biochemical parameters, though not all, but at least in part were closely correlated with RRF in peritoneal dialysis patients.

  19. Disruption of key NADH-binding pocket residues of the Mycobacterium tuberculosis InhA affects DD-CoA binding ability.

    Science.gov (United States)

    Shaw, Daniel J; Robb, Kirsty; Vetter, Beatrice V; Tong, Madeline; Molle, Virginie; Hunt, Neil T; Hoskisson, Paul A

    2017-07-05

    Tuberculosis (TB) is a global health problem that affects over 10 million people. There is an urgent need to develop novel antimicrobial therapies to combat TB. To achieve this, a thorough understanding of key validated drug targets is required. The enoyl reductase InhA, responsible for synthesis of essential mycolic acids in the mycobacterial cell wall, is the target for the frontline anti-TB drug isoniazid. To better understand the activity of this protein a series of mutants, targeted to the NADH co-factor binding pocket were created. Residues P193 and W222 comprise a series of hydrophobic residues surrounding the cofactor binding site and mutation of both residues negatively affect InhA function. Construction of an M155A mutant of InhA results in increased affinity for NADH and DD-CoA turnover but with a reduction in V max for DD-CoA, impairing overall activity. This suggests that NADH-binding geometry of InhA likely permits long-range interactions between residues in the NADH-binding pocket to facilitate substrate turnover in the DD-CoA binding region of the protein. Understanding the precise details of substrate binding and turnover in InhA and how this may affect protein-protein interactions may facilitate the development of improved inhibitors enabling the development of novel anti-TB drugs.

  20. Disruptions in cortico-subcortical covariance networks associated with anxiety in new-onset childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Camille Garcia-Ramos

    2016-01-01

    Full Text Available Anxiety disorders represent a prevalent psychiatric comorbidity in both adults and children with epilepsy for which the etiology remains controversial. Neurobiological contributions have been suggested, but only limited evidence suggests abnormal brain volumes particularly in children with epilepsy and anxiety. Since the brain develops in an organized fashion, covariance analyses between different brain regions can be investigated as a network and analyzed using graph theory methods. We examined 46 healthy children (HC and youth with recent onset idiopathic epilepsies with (n = 24 and without (n = 62 anxiety disorders. Graph theory (GT analyses based on the covariance between the volumes of 85 cortical/subcortical regions were investigated. Both groups with epilepsy demonstrated less inter-modular relationships in the synchronization of cortical/subcortical volumes compared to controls, with the epilepsy and anxiety group presenting the strongest modular organization. Frontal and occipital regions in non-anxious epilepsy, and areas throughout the brain in children with epilepsy and anxiety, showed the highest centrality compared to controls. Furthermore, most of the nodes correlating to amygdala volumes were subcortical structures, with the exception of the left insula and the right frontal pole, which presented high betweenness centrality (BC; therefore, their influence in the network is not necessarily local but potentially influencing other more distant regions. In conclusion, children with recent onset epilepsy and anxiety demonstrate large scale disruptions in cortical and subcortical brain regions. Network science may not only provide insight into the possible neurobiological correlates of important comorbidities of epilepsy, but also the ways that cortical and subcortical disruption occurs.

  1. Production of bioethanol and associated by-products from potato starch residue stream by Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Hashem, Mohamed [King Khalid University, Faculty of Science, Biological Science Department, P.O. Box 10255, Abha 61321 (Saudi Arabia); Darwish, Soumia M.I. [Department of Food Science and Technology, Faculty of Agriculture, Assiut University (Egypt)

    2010-07-15

    Potato starch residue stream produced during chips manufacturing was used as an economical source for biomass and bioethanol production by Saccharomyces cerevisiae. Results demonstrated that 1% H{sub 2}SO{sub 4} at 100 C for 1 h was enough to hydrolyze all starch contained in the residue stream. Two strains of S. cerevisiae (y-1646 and commercial one) were able to utilize and ferment the acid-treated residue stream under both aerobic and semi-anaerobic conditions. The maximum yield of ethanol (5.52 g L{sup -1}) was achieved at 35 C by S. cerevisiae y-1646 after 36 h when ZnCl{sub 2} (0.4 g L{sup -1}) was added. Addition of NH{sub 4}NO{sub 3} as a source of nitrogen did not significantly affect either growth or ethanol production by S. cerevisiae y-1646. Some secondary by-products including alcohol derivatives and medical active compound were found to be associated with the ethanol production process. (author)

  2. Structural disruption of the dorsal cingulum bundle is associated with impaired Stroop performance in patients with schizophrenia.

    Science.gov (United States)

    Takei, Kunio; Yamasue, Hidenori; Abe, Osamu; Yamada, Haruyasu; Inoue, Hideyuki; Suga, Motomu; Muroi, Miya; Sasaki, Hiroki; Aoki, Shigeki; Kasai, Kiyoto

    2009-10-01

    Previous diffusion tensor imaging (DTI) studies have shown structural abnormalities of the cingulum bundle (CB) in patients with schizophrenia. However, regional specificity and functional relevance of the pregenual and dorsal CB subdivisions has not been fully studied. In the current study, 31 patients with schizophrenia and 65 age- and gender-matched healthy subjects underwent DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) in cross sections of dorsal and pregenual CB tractography. To test the hypothesis of region-specific association with neurocognition, all of the patients and 31 controls performed the Stroop task, which is assumed to mainly involve dorsal cingulate function. The verbal memory subscale of Wechsler Memory Scale-Revised and premorbid IQs estimated from the Japanese version of the National Adult Reading Test, which were non-specific to dorsal cingulate function, were also employed as control neurocognitive indices. Significant bilateral FA reductions in the pregenual and dorsal CB, and bilateral MD increases in the dorsal CB were observed in the patients compared with the controls. As predicted, significant associations between DTI measures and neurocognition were found in the schizophrenia group only: double-dissociable correlation between higher MD in the dorsal, not in the pregenual CB, and a longer reaction time in the Stroop task, not verbal memory or premorbid IQs. The current DTI study suggests that structural disruption of the dorsal CB has region-specific functional relevance to selective attention deficits, although structural disruption also exists in the pregenual CB in patients with schizophrenia.

  3. Disrupted topological organization of brain structural network associated with prior overt hepatic encephalopathy in cirrhotic patients

    International Nuclear Information System (INIS)

    Chen, Hua-Jun; Shi, Hai-Bin; Jiang, Long-Feng; Li, Lan; Chen, Rong

    2018-01-01

    To investigate structural brain connectome alterations in cirrhotic patients with prior overt hepatic encephalopathy (OHE). Seventeen cirrhotic patients with prior OHE (prior-OHE), 18 cirrhotic patients without prior OHE (non-prior-OHE) and 18 healthy controls (HC) underwent diffusion tensor imaging. Neurocognitive functioning was assessed with Psychometric Hepatic Encephalopathy Score (PHES). Using a probabilistic fibre tracking approach, we depicted the whole-brain structural network as a connectivity matrix of 90 regions (derived from the Automated Anatomic Labeling atlas). Graph theory-based analyses were performed to analyse topological properties of the brain network. The analysis of variance showed significant group effects on several topological properties, including network strength, global efficiency and local efficiency. A progressive decrease trend for these metrics was found from non-prior-OHE to prior-OHE, compared with HC. Among the three groups, the regions with altered nodal efficiency were mainly distributed in the frontal and occipital cortices, paralimbic system and subcortical regions. The topological metrics, such as network strength and global efficiency, were correlated with PHES among cirrhotic patients. The cirrhotic patients developed structural brain connectome alterations; this is aggravated by prior OHE episode. Disrupted topological organization of the brain structural network may account for cognitive impairments related to prior OHE. (orig.)

  4. Disruptive behavior disorders in offspring of parents with major depression: associations with parental behavior disorders.

    Science.gov (United States)

    Hirshfeld-Becker, Dina R; Petty, Carter; Micco, Jamie A; Henin, Aude; Park, Jennifer; Beilin, Ari; Rosenbaum, Jerrold F; Biederman, Joseph

    2008-12-01

    Although the offspring of parents with major depressive disorder (MDD) are at increased risk to develop disruptive behavior disorders (DBD) in addition to MDD, it remains unclear whether this heightened risk is due to MDD or to comorbid DBD in the parents. In a secondary analysis of longitudinal data from offspring at risk for MDD and panic disorder and comparison children, we stratified 169 children of parents who had been treated for MDD based upon presence (n=50) or absence (n=119) of parental history of DBD (ADHD, oppositional disorder, and conduct disorder) and contrasted them with children of parents with DBD but without MDD (n=19) and children whose parents had neither MDD nor DBD (n=106). The children had been assessed in middle childhood using structured diagnostic interviews. Offspring of parents with MDD + DBD had significantly higher rates of MDD, DBD in general, and ADHD in particular, compared with offspring of parents with MDD alone. Offspring of parents with MDD + DBD also had higher rates of mania than controls. Both parental MDD and DBD conferred independent risk for MDD and DBD in the offspring. However, only parental DBD conferred independent risk for conduct disorder and ADHD and only parental MDD conferred independent risk for oppositional defiant disorder. Elevated rates of DBD in the offspring of parents with MDD appear to be due in part to the presence of DBD in the parents. Further studies of samples not selected on the basis of parental panic disorder are needed to confirm these results.

  5. Association between Endocrine Disrupting Phenols in Colostrums and Maternal and Infant Health

    Directory of Open Access Journals (Sweden)

    B. Yi

    2013-01-01

    Full Text Available Bisphenol A (BPA and alkylphenols (APs are well-known endocrine disrupting chemicals (EDCs which may threat the next generations' health. We performed biomonitoring of these phenols in colostrums to assess risk of the phenols in breast-fed neonates. Study subjects were the lactating mothers who delivered babies within 2 weeks (N=325; 30.67 ± 3.45 years and their neonates (N=326; embryonic period, 39.1 ± 1.5 weeks. BPA, nonylphenol (NP, and octylphenol (OP in colostrums were quantified with LC/MS/MS. Information for environmental exposure sources of the phenols was obtained by questionnaires. As results, median level of BPA in colostrums was 7.8 ng/mL, while most NP or OP was not detected. Regarding health risks of phenols, levels of total NP in colostrums were elevated among sick mothers with toxemia, thyroid disorders, gastritis, and so forth than health mothers (3.51 ± 4.98 versus 2.04 ± 3.71 ng/mL, P=0.02. Dairy products intake and detergents use were positively correlated with total BPA levels (Ps<0.05. In conclusion, we estimate most neonates who are exposed to BPA rather than NP or OP via colostrums and recommend continuous biomonitoring of the phenols to clarify their suspected health risk on neonates and pregnant or gestation mothers.

  6. Disrupted topological organization of brain structural network associated with prior overt hepatic encephalopathy in cirrhotic patients

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hua-Jun [Fujian Medical University Union Hospital, Department of Radiology, Fuzhou (China); The First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing (China); Shi, Hai-Bin [The First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing (China); Jiang, Long-Feng [The First Affiliated Hospital of Nanjing Medical University, Department of Infectious Diseases, Nanjing (China); Li, Lan [Fujian Medical University Union Hospital, Department of Radiology, Fuzhou (China); Chen, Rong [University of Maryland School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Baltimore, MD (United States); Beijing Institute of Technology, Advanced Innovation Center for Intelligent Robots and Systems, Beijing (China)

    2018-01-15

    To investigate structural brain connectome alterations in cirrhotic patients with prior overt hepatic encephalopathy (OHE). Seventeen cirrhotic patients with prior OHE (prior-OHE), 18 cirrhotic patients without prior OHE (non-prior-OHE) and 18 healthy controls (HC) underwent diffusion tensor imaging. Neurocognitive functioning was assessed with Psychometric Hepatic Encephalopathy Score (PHES). Using a probabilistic fibre tracking approach, we depicted the whole-brain structural network as a connectivity matrix of 90 regions (derived from the Automated Anatomic Labeling atlas). Graph theory-based analyses were performed to analyse topological properties of the brain network. The analysis of variance showed significant group effects on several topological properties, including network strength, global efficiency and local efficiency. A progressive decrease trend for these metrics was found from non-prior-OHE to prior-OHE, compared with HC. Among the three groups, the regions with altered nodal efficiency were mainly distributed in the frontal and occipital cortices, paralimbic system and subcortical regions. The topological metrics, such as network strength and global efficiency, were correlated with PHES among cirrhotic patients. The cirrhotic patients developed structural brain connectome alterations; this is aggravated by prior OHE episode. Disrupted topological organization of the brain structural network may account for cognitive impairments related to prior OHE. (orig.)

  7. Portal vein thrombosis in cirrhosis is not associated with intestinal barrier disruption or increased platelet aggregability.

    Science.gov (United States)

    Wosiewicz, Piotr; Żorniak, Michał; Hartleb, Marek; Barański, Kamil; Hartleb, Maciej; Onyszczuk, Magdalena; Pilch-Kowalczyk, Joanna; Kyrcz-Krzemień, Sławomira

    2016-12-01

    Portal vein thrombosis (PVT) is a common complication of cirrhosis, but its pathogenesis is unclear. We tested the hypotheses that PVT is the result of platelet hyperactivity or intestinal barrier disruption. This study included 49 patients with cirrhosis (15 females) of mixed etiology. Based on spiral computed-tomography, the patients were divided into two groups: with PVT (n=16) and without PVT (n=33). Serum biomarkers of intestinal barrier integrity were endotoxins and zonulin, and platelet activity was assessed with multiple electrode aggregometry. The levels of endotoxin (43.5±18.3ng/ml vs. 36.9±7.5ng/ml; P=0.19) and zonulin (56.3±31.1ng/ml vs. 69.3±63.1ng/ml; P=0.69) were not different between the patients with and without PVT. Moreover, endotoxin and zonulin did not correlate with the coagulation and platelet parameters. The platelet aggregability measured with the TRAP and the ADP tests was decreased in PVT patients. In the logistic regression analysis the PVT incidence was related to the levels of D-dimer and bilirubin as well as the TRAP test results. Patients with PVT presented with significantly higher levels of D-dimer (4.45±2.59 vs. 3.03±2.97mg/l; P<0.05) and prothrombin levels (175±98.8μg/ml vs. 115±72.9μg/ml; P<0.05) than patients without thrombosis. PVT could be excluded with a 90% negative predictive value when the D-dimer level was below 1.82mg/l. Endotoxemia and platelet activity are not determinants of PVT in patients with cirrhosis. The D-dimer measurement has diagnostic significance for PVT in patients with liver cirrhosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Residue level description of in vivo self-association of Plasmodium falciparum P2.

    Science.gov (United States)

    Mishra, Pushpa; Sharma, Shobhona; Hosur, Ramakrishna V

    2014-04-01

    Plasmodium falciparum P2 (PfP2) is a ribosomal stalk protein. It also performs extra ribosomal novel functions that seem to be associated with homo oligomerization . Previous in vitro studies have demonstrated that the protein has a high tendency to self-associate predominantly into an 8-mer. In vitro Heteronuclear Single Quantum Coherence (HSQC) of the pure recombinant protein (rPfP2) and its in-cell (Escherichia coli) HSQC spectrum has very similar features, indicating that the protein intrinsically, both inside the cell and under in vitro conditions, has similar aggregation tendencies. In view of this, we have characterized here the folding and concomitant self-association of rPfP2, using an in vitro dissociation-association strategy. We observed that the residue stretch, (Met31-Leu44) of the rPfP2, mapping to Met1-Leu14 of PfP2 protein acts as a nucleation site for helix formation and subsequent self-association. Further association appears to be driven by hydrophobic and complimentary electrostatic charge interactions on the surfaces formed. One stretch of rPfP2, (Ile97-Ala116), always remains floppy, and this may serve as "hinge" for protein segmental motions. Based on these, we have proposed a possible model for rPfP2 self-association into an 8-mer.

  9. Investigating Disruption

    DEFF Research Database (Denmark)

    Lundgaard, Stine Schmieg; Rosenstand, Claus Andreas Foss

    This book shares knowledge collected from 2015 and onward within the Consortium for Digital Disruption anchored at Aalborg University (www.dd.aau.dk). Evidenced by this publication, the field of disruptive innovation research has gone through several stages of operationalizing the theory. In recent...... years, researchers are increasingly looking back towards the origins of the theory in attempts to cure it from its most obvious flaws. This is especially true for the use of the theory in making predictions about future disruptions. In order to continue to develop a valuable theory of disruption, we...... find it useful to first review what the theory of disruptive innovation initially was, how it has developed, and where we are now. A cross section of disruptive innovation literature has been reviewed in order to form a general foundation from which we might better understand the changing world...

  10. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies.

    Science.gov (United States)

    Kim, Hyung-Goo; Kim, Hyun-Taek; Leach, Natalia T; Lan, Fei; Ullmann, Reinhard; Silahtaroglu, Asli; Kurth, Ingo; Nowka, Anja; Seong, Ihn Sik; Shen, Yiping; Talkowski, Michael E; Ruderfer, Douglas; Lee, Ji-Hyun; Glotzbach, Caron; Ha, Kyungsoo; Kjaergaard, Susanne; Levin, Alex V; Romeike, Bernd F; Kleefstra, Tjitske; Bartsch, Oliver; Elsea, Sarah H; Jabs, Ethylin Wang; MacDonald, Marcy E; Harris, David J; Quade, Bradley J; Ropers, Hans-Hilger; Shaffer, Lisa G; Kutsche, Kerstin; Layman, Lawrence C; Tommerup, Niels; Kalscheuer, Vera M; Shi, Yang; Morton, Cynthia C; Kim, Cheol-Hee; Gusella, James F

    2012-07-13

    Potocki-Shaffer syndrome (PSS) is a contiguous gene disorder due to the interstitial deletion of band p11.2 of chromosome 11 and is characterized by multiple exostoses, parietal foramina, intellectual disability (ID), and craniofacial anomalies (CFAs). Despite the identification of individual genes responsible for multiple exostoses and parietal foramina in PSS, the identity of the gene(s) associated with the ID and CFA phenotypes has remained elusive. Through characterization of independent subjects with balanced translocations and supportive comparative deletion mapping of PSS subjects, we have uncovered evidence that the ID and CFA phenotypes are both caused by haploinsufficiency of a single gene, PHF21A, at 11p11.2. PHF21A encodes a plant homeodomain finger protein whose murine and zebrafish orthologs are both expressed in a manner consistent with a function in neurofacial and craniofacial development, and suppression of the latter led to both craniofacial abnormalities and neuronal apoptosis. Along with lysine-specific demethylase 1 (LSD1), PHF21A, also known as BHC80, is a component of the BRAF-histone deacetylase complex that represses target-gene transcription. In lymphoblastoid cell lines from two translocation subjects in whom PHF21A was directly disrupted by the respective breakpoints, we observed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional regulation. Our finding that disruption of PHF21A by translocations in the PSS region is associated with ID adds to the growing list of ID-associated genes that emphasize the critical role of transcriptional regulation and chromatin remodeling in normal brain development and cognitive function. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  11. Coral-associated bacteria, quorum sensing disrupters, and the regulation of biofouling.

    Science.gov (United States)

    Golberg, Karina; Pavlov, Valentina; Marks, Robert S; Kushmaro, Ariel

    2013-01-01

    Marine biofouling, the settlement of microorganisms and macroorganisms on structures submerged in seawater, although economically detrimental, is a successful strategy for survival in hostile environments, where coordinated bacterial communities establish biofilms via the regulation of quorum sensing (QS) communication systems. The inhibition of QS activity among bacteria isolated from different coral species was investigated to gain further insight into its potency in the attenuation, or even the prevention, of undesirable biofouling on marine organisms. It is hypothesized that coral mucus/microorganism interactions are competitive, suggesting that the dominant communities secrete QS disruptive compounds. One hundred and twenty bacterial isolates were collected from healthy coral species and screened for their ability to inhibit QS using three bioreporter strains. Approximately 12, 11, and 24% of the isolates exhibited anti-QS activity against Escherichia coli pSB1075, Chromobacterium violaceum CV026, and Agrobacterium tumefaciens KYC55 indicator strains, respectively. Isolates with positive activity against the bioluminescent monitor strains were scanned via a cytotoxic/genotoxic, E. coli TV1061 and DPD2794 antimicrobial panel. Isolates detected by C. violaceum CV026 and A. tumefaciens KYC55 reporter strains were tested for their ability to inhibit the growth of these reporter strains, which were found to be unaffected. Tests of the Favia sp. coral isolate Fav 2-50-7 (>98% similarity to Vibrio harveyi) for its ability to attenuate the formation of biofilm showed extensive inhibitory activity against biofilms of Pseudomonas aeruginosa and Acinetobacter baumannii. To ascertain the stability and general structure of the active compound, cell-free culture supernatants exposed to an increasing temperature gradient or to digestion by proteinase K, were shown to maintain potent QS attenuation and the ability to inhibit the growth of biofilms. Mass spectrometry confirmed

  12. Cold hands, warm feet: sleep deprivation disrupts thermoregulation and its association with vigilance

    NARCIS (Netherlands)

    Romeijn, N.; Verweij, I.M.; Koeleman, A.; Mooij, A.; Steimke, R.; Virkkala, J.; van der Werf, Y.D.; van Someren, E.J.W.

    2012-01-01

    Study Objectives: Vigilance is affected by induced and spontaneous skin temperature fluctuations. Whereas sleep deprivation strongly affects vigilance, no previous study examined in detail its effect on human skin temperature fluctuations and their association with vigilance. Design: In a

  13. The roots of stereotype threat: when automatic associations disrupt girls' math performance.

    Science.gov (United States)

    Galdi, Silvia; Cadinu, Mara; Tomasetto, Carlo

    2014-01-01

    Although stereotype awareness is a prerequisite for stereotype threat effects (Steele & Aronson, 1995), research showed girls' deficit under stereotype threat before the emergence of math-gender stereotype awareness, and in the absence of stereotype endorsement. In a study including 240 six-year-old children, this paradox was addressed by testing whether automatic associations trigger stereotype threat in young girls. Whereas no indicators were found that children endorsed the math-gender stereotype, girls, but not boys, showed automatic associations consistent with the stereotype. Moreover, results showed that girls' automatic associations varied as a function of a manipulation regarding the stereotype content. Importantly, girls' math performance decreased in a stereotype-consistent, relative to a stereotype-inconsistent, condition and automatic associations mediated the relation between stereotype threat and performance. © 2013 The Authors. Child Development © 2013 Society for Research in Child Development, Inc.

  14. Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European union

    DEFF Research Database (Denmark)

    Bellanger, Martine; Demeneix, Barbara; Grandjean, Philippe

    2015-01-01

    CONTEXT: Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. OBJECTIVE: The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably...... peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients...... by multiple EDCs was assigned a 20-69% probability, with 19 300 to 31 200 attributable cases at a cost of €1.21 billion to €2.86 billion. CONCLUSIONS: EDC exposures in Europe contribute substantially to neurobehavioral deficits and disease, with a high probability of >€150 billion costs/year. These results...

  15. Sulforaphane inhibits pancreatic cancer through disrupting Hsp90-p50(Cdc37) complex and direct interactions with amino acids residues of Hsp90.

    Science.gov (United States)

    Li, Yanyan; Karagöz, G Elif; Seo, Young Ho; Zhang, Tao; Jiang, Yiqun; Yu, Yanke; Duarte, Afonso M S; Schwartz, Steven J; Boelens, Rolf; Carroll, Kate; Rüdiger, Stefan G D; Sun, Duxin

    2012-12-01

    Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl) butane)], an isothiocyanate derived from cruciferous vegetables, has been shown to possess potent chemopreventive activity. We analyzed the effect of sulforaphane on the proliferation of pancreatic cancer cells. Sulforaphane inhibited pancreatic cancer cell growth in vitro with IC(50)s of around 10-15 μM and induced apoptosis. In pancreatic cancer xenograft mouse model, administration of sulforaphane showed remarkable inhibition of tumor growth without apparent toxicity noticed. We found that sulforaphane induced the degradation of heat shock protein 90 (Hsp90) client proteins and blocked the interaction of Hsp90 with its cochaperone p50(Cdc37) in pancreatic cancer cells. Using nuclear magnetic resonance spectroscopy (NMR) with an isoleucine-specific labeling strategy, we overcame the protein size limit of conventional NMR and studied the interaction of sulforaphane with full-length Hsp90 dimer (170 kDa) in solution. NMR revealed multiple chemical shifts in sheet 2 and the adjacent loop in Hsp90 N-terminal domain after incubation of Hsp90 with sulforaphane. Liquid chromatography coupled to mass spectrometry further mapped a short peptide in this region that was tagged with sulforaphane. These data suggest a new mechanism of sulforaphane that disrupts protein-protein interaction in Hsp90 complex for its chemopreventive activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Sulforaphane inhibits pancreatic cancer through disrupting Hsp90-p50Cdc37 complex and direct interactions with amino acids residues of Hsp90

    Science.gov (United States)

    Li, Yanyan; Karagöz, G. Elif; Seo, Young Ho; Zhang, Tao; Jiang, Yiqun; Yu, Yanke; Duarte, Afonso M.S.; Schwartz, Steven J.; Boelens, Rolf; Carroll, Kate; Rüdiger, Stefan G. D.; Sun, Duxin

    2011-01-01

    Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl) butane)], an isothiocyanate derived from cruciferous vegetables, has been shown to possess potent chemopreventive activity. We analyzed the effect of sulforaphane on the proliferation of pancreatic cancer cells. Sulforaphane inhibited pancreatic cancer cell growth in vitro with the IC50's around 10-15 μM and induced apoptosis. In pancreatic cancer xenograft mouse model, administration of sulforaphane showed remarkable inhibition of tumor growth without apparent toxicity noticed. We found that sulforaphane induced the degradation of heat shock protein 90 (Hsp90) client proteins and blocked the interaction of Hsp90 with its cochaperone p50Cdc37 in pancreatic cancer cells. Using Nuclear Magnetic Resonance Spectroscopy (NMR) with an isoleucine-specific labeling strategy, we overcame the protein size limit of conventional NMR and studied the interaction of sulforaphane with full-length Hsp90 dimer (170 kDa) in solution. NMR revealed multiple chemical shifts in sheet 2 and the adjacent loop in Hsp90 N-terminal domain after incubation of Hsp90 with sulforaphane. Liquid Chromatography coupled to Mass Spectrometry (LC-MS) further mapped a short peptide in this region that was tagged with sulforaphane. These data suggest a new mechanism of sulforaphane that disrupts protein-protein interaction in Hsp90 complex for its chemopreventive activity. PMID:22444872

  17. Clinical residual symptomatology and associated factors in multiple organ failure survivors: A long-term mortgage.

    Science.gov (United States)

    Rodríguez-Villar, S; Rodríguez-García, J L; Arévalo-Serrano, J; Sánchez-Casado, M; Fletcher, H

    2017-12-01

    To evaluate which residual clinical symptoms multi-organ failure (MOF) patients may exhibit post discharge from Intensive Care Units (ICU) and to identify the associated factors that cause such symptoms. A total of 545 adult patients admitted to a medical & surgical ICU in Spain diagnosed with MOF on admission were included in the study. Follow up in the form of a telephone survey regarding the patients clinical symptoms were conducted at 6 and 12 months after discharge from ICU. A total of 266 patients were followed up at both 6 and 12 months post ICU discharge; 62.2% were male; age 60±18 years; 67.8% medical patients. The most common symptoms to appear following hospital discharge included: asthenia (173; 76%), sleep disturbances (112; 50%) and depression (109; 48%). The study revealed frequent residual clinical symptoms persisting for almost a year post ICU discharge, most notably arthromyalgia and asthenia. Depression symptoms during the first 6 months post-hospital discharge were also common among multiple organ failure survivors. The presence of symptomatology over time was found to be related to a poor functional situation at 6 and12 months post ICU discharge, length of hospital stay and severity of illness score on ICU admission. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. All rights reserved.

  18. Systemic Associations with Residual Subretinal Fluid after Ranibizumab in Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Meng-Ju Tsai

    2017-01-01

    Full Text Available Purpose. To investigate the impact of systemic diseases on the occurrence of subretinal fluid (SRF in diabetic macular edema (DME and prognostic factors for residual SRF following three consecutive monthly intravitreal ranibizumab. Methods. Ninety-seven eyes from 68 patients with DME who completed 3 consecutive monthly injections of ranibizumab were enrolled. Systemic parameters mainly included chronic kidney disease (CKD, hypertension, HbA1c, and insulin dependence. Renal parameters for CKD were serum creatinine, estimated glomerular filtration rate (eGFR, and serum albumin. Ocular factors were baseline central macular thickness (CMT, severity of diabetic retinopathy (DR, and status of panretinal photocoagulation (PRP. Results. Chronic kidney disease had significant correlation with baseline SRF (R=0.397, p<0.001 after partial correlation with adjustment for age and DR severity. As for CKD, lower serum albumin, but not eGFR or serum creatinine, was associated with baseline presence of SRF (p=0.026, p=0.08 and p=0.53, resp., after adjustment for age and DR severity. Overall, lower eGFR and lower HbA1c values, contrary to popular belief, predicted the presence of residual SRF following intravitreal injections (p=0.016 and p<0.001, resp.. Conclusions. Tight sugar control and poorer baseline kidney function may slow the resorption of SRF after anti-VEGF injections in patients with DME in the short term.

  19. Disruption model

    International Nuclear Information System (INIS)

    Murray, J.G.; Bronner, G.

    1982-07-01

    Calculations of disruption time and energy dissipation have been obtained by simulating the plasma as an electrical conducting loop that varies in resistivity, current density, major radius. The calculations provide results which are in good agreement with experimental observations. It is believed that this approach allows engineering designs for disruptions to be completed in large tokamaks such as INTOR or FED

  20. FABP4 is a leading candidate gene associated with residual feed intake in growing Holstein calves.

    Science.gov (United States)

    Cohen-Zinder, Miri; Asher, Aviv; Lipkin, Ehud; Feingersch, Roi; Agmon, Rotem; Karasik, David; Brosh, Arieh; Shabtay, Ariel

    2016-05-01

    Ecological and economic concerns drive the need to improve feed utilization by domestic animals. Residual feed intake (RFI) is one of the most acceptable measures for feed efficiency (FE). However, phenotyping RFI-related traits is complex and expensive and requires special equipment. Advances in marker technology allow the development of various DNA-based selection tools. To assimilate these technologies for the benefit of RFI-based selection, reliable phenotypic measures are prerequisite. In the current study, we identified single nucleotide polymorphisms (SNPs) associated with RFI phenotypic consistency across different ages and diets (named RFI 1-3), using DNA samples of high or low RFI ranked Holstein calves. Using targeted sequencing of chromosomal regions associated with FE- and RFI-related traits, we identified 48 top SNPs significantly associated with at least one of three defined RFIs. Eleven of these SNPs were harbored by the fatty acid binding protein 4 (FABP4). While 10 significant SNPs found in FABP4 were common for RFI 1 and RFI 3, one SNP (FABP4_5; Aassociated with all three RFIs. As the three RFI classes reflect changing diets and ages with concomitant RFI phenotypic consistency, the above polymorphisms and in particular FABP4_5, might be considered possible markers for RFI-based selection for FE in the Holstein breed, following a larger-scale validation. Copyright © 2016 the American Physiological Society.

  1. Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia.

    Science.gov (United States)

    Tsakogiannis, D; Gortsilas, P; Kyriakopoulou, Z; Ruether, I G A; Dimitriou, T G; Orfanoudakis, G; Markoulatos, P

    2015-11-01

    Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or E2 genes. The present study investigated the disruption of E1, E2 genes in a total of eighty four HPV16-positive precancerous and cervical cancer specimens derived from Greek women (seventeen paraffin-embedded cervical biopsies and sixty seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and nine overlapping primer sets respectively, in order to define the sites of disruption. Extensive mapping analysis revealed that disruption/deletion events within E2 gene occurred in high grade and cervical cancer samples (x(2) test, P disruption was documented among low grade cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene occur both in high and low grade cervical intraepithelial neoplasia. This leads to the assumption that in low grade cervical intraepithelial neoplasias only E1 gene disruption was involved (Fisher's exact test, P disruption of E1 gene was located between nucleotides 1059 and 1323, while the most prevalent deleted region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge region). Therefore, it is proposed that each population has its own profile of frequencies and sites of disruptions and extensive mapping analysis of E1 and E2 genes is mandatory in order to determine suitable markers for HPV16 DNA integration analysis in distinct populations. © 2015 Wiley Periodicals, Inc.

  2. Functional variant disrupts insulin induction of USF1: mechanism for USF1-associated dyslipidemias

    DEFF Research Database (Denmark)

    Naukkarinen, J.; Nilsson, E.; Koistinen, H.A.

    2009-01-01

    BACKGROUND: The upstream transcription factor 1 (USF1) gene is associated with familial combined hyperlipidemia, the most common genetic dyslipidemia in humans, as well as with various dyslipidemic changes in numerous other studies. Typical of complex disease-associated genes, neither the explicit...... in USF1 is involved in the development of dyslipidemia. The effects of the risk variant on gene expression were studied in 2 relevant human tissues, fat and muscle. Global transcript profiles of 47 fat biopsies ascertained for carriership of the risk allele were tested for differential expression......, a defective response of USF1 to insulin results in the suboptimal response of relevant target genes that contributes to the enhanced risk of developing dyslipidemia and coronary heart disease Udgivelsesdato: 2009/10...

  3. Disruption of paired-associate learning in rat offspring perinatally exposed to dioxins.

    Science.gov (United States)

    Kakeyama, Masaki; Endo, Toshihiro; Zhang, Yan; Miyazaki, Wataru; Tohyama, Chiharu

    2014-03-01

    The prevalence of cognitive abnormalities in children has partly been ascribed to environmental chemical exposure. Appropriate animal models and tools for evaluating higher brain function are required to examine this problem. A recently developed behavioral test in which rats learn six unique flavor-location pairs in a test arena was used to evaluate paired-associate learning, a hallmark of the higher cognitive function that is essential to language learning in humans. Pregnant Long-Evans rats were dosed by gavage with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) at a dose of 0, 200, or 800 ng/kg (referred as Control, TCDD-200, TCDD-800, TBDD-200, or TBDD-800, hereafter) on gestational day 15, and the offspring was tested during adulthood. Paired-associate learning was found to be impaired in the TCDD-200 and TBDD-200 groups, but not in either group exposed to 800 ng/kg, the observations of which were ensured by non-cued trials. As for the emotional aspect, during habituation, the TCDD-200 and TBDD-200 groups showed significantly longer latencies to enter the test arena from a start box than the Control, TCDD-800, and TBDD-800 groups, suggesting that the TCDD-200 and TBDD-200 groups manifested anxiety-like behavior. Thus, both the chlorinated dioxin and its brominated congener affected higher brain function to a similar extent in a nearly identical manner. Use of the behavioral test that can evaluate paired-associate learning in rats demonstrated that in utero and lactational exposure to not only TCDD but also TBDD perturbed higher brain function in rat offspring in a nonmonotonic manner.

  4. Mild maternal stress disrupts associative learning and increases aggression in offspring.

    Science.gov (United States)

    Eaton, L; Edmonds, E J; Henry, T B; Snellgrove, D L; Sloman, K A

    2015-05-01

    Maternal stress has been shown to affect behaviour of offspring in a wide range of animals, but this evidence has come from studies that exposed gestating mothers to acute or severe stressors, such as restraint or exposure to synthetic stress hormones. Here we show that exposure of mothers to even a mild stressor reduces associative learning and increases aggression in offspring. Female guppies were exposed to routine husbandry procedures that produced only a minimal, non-significant, elevation of the stress hormone cortisol. In contrast to controls, offspring from mothers that experienced this mild stress failed to learn to associate a colour cue and food reward, and showed a greater amount of inter-individual variation in behaviour compared with control offspring. This mild stress also resulted in offspring that were more aggressive towards their own mirror image than controls. While it is possible that these results could represent the transmission of beneficial maternal characteristics to offspring born into unpredictable environments, the potential for mild maternal stress to affect offspring performance also has important implications for research into the trans-generational effects of stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Evidence for association between Disrupted-in-schizophrenia 1 (DISC1 gene polymorphisms and autism in Chinese Han population: a family-based association study

    Directory of Open Access Journals (Sweden)

    Ruan Yan

    2011-05-01

    Full Text Available Abstract Background Disrupted-in-Schizophrenia 1 (DISC1 gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. Methods We genotyped seven tag single nucleotide polymorphisms (SNPs in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT and Haploview software. Results We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02. After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values. Conclusions Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.

  6. Small Molecule Disrupts Abnormal Gene Fusion Associated with Leukemia | Center for Cancer Research

    Science.gov (United States)

    Rare chromosomal abnormalities, called chromosomal translocations, in which part of a chromosome breaks off and becomes attached to another chromosome, can result in the generation of chimeric proteins. These aberrant proteins have unpredictable, and sometimes harmful, functions, including uncontrolled cell growth that can lead to cancer. One type of translocation, in which a portion of the gene encoding nucleoporin 98 (NUP98)—one of about 50 proteins comprising the nuclear pore complex through which proteins are shuttled into and out of the nucleus—fuses with another gene, has been shown to result in improper histone modifications. These abnormalities alter the gene expression patterns of certain types of hematopoietic, or blood-forming, stem cells, resulting primarily in overexpression of the Hoxa7, Hoxa9,and Hoxa10 genes. NUP98 chromosomal translocations have been associated with many types of leukemia, including acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia in blast crisis (CML-bc), and myelodysplastic syndrome (MDS).

  7. Gender differences in oxytocin-associated disruption of decision bias during emotion perception.

    Science.gov (United States)

    Lynn, Spencer K; Hoge, Elizabeth A; Fischer, Laura E; Barrett, Lisa Feldman; Simon, Naomi M

    2014-09-30

    Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocin׳s effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocin׳s effect on emotion perception and might explain inconsistent results across studies. Of relevance, studies of oxytocin׳s effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein bias to categorize faces as angry would maximize point earnings. Consistent with an underestimation of the factors creating risk (i.e., encounter rate and cost), men given oxytocin exhibited a worse (i.e., less liberal) response bias than men given placebo. Oxytocin did not influence women׳s performance. These results suggest that oxytocin may impair men׳s ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Antisense oligonucleotide therapy rescues disruptions in organization of exploratory movements associated with Usher syndrome type 1C in mice.

    Science.gov (United States)

    Donaldson, Tia N; Jennings, Kelsey T; Cherep, Lucia A; McNeela, Adam M; Depreux, Frederic F; Jodelka, Francine M; Hastings, Michelle L; Wallace, Douglas G

    2018-02-15

    Usher syndrome, Type 1C (USH1C) is an autosomal recessive inherited disorder in which a mutation in the gene encoding harmonin is associated with multi-sensory deficits (i.e., auditory, vestibular, and visual). USH1C (Usher) mice, engineered with a human USH1C mutation, exhibit these multi-sensory deficits by circling behavior and lack of response to sound. Administration of an antisense oligonucleotide (ASO) therapeutic that corrects expression of the mutated USH1C gene, has been shown to increase harmonin levels, reduce circling behavior, and improve vestibular and auditory function. The current study evaluates the organization of exploratory movements to assess spatial organization in Usher mice and determine the efficacy of ASO therapy in attenuating any such deficits. Usher and heterozygous mice received the therapeutic ASO, ASO-29, or a control, non-specific ASO treatment at postnatal day five. Organization of exploratory movements was assessed under dark and light conditions at two and six-months of age. Disruptions in exploratory movement organization observed in control-treated Usher mice were consistent with impaired use of self-movement and environmental cues. In general, ASO-29 treatment rescued organization of exploratory movements at two and six-month testing points. These observations are consistent with ASO-29 rescuing processing of multiple sources of information and demonstrate the potential of ASO therapies to ameliorate topographical disorientation associated with other genetic disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed.

    Science.gov (United States)

    Forman, Oliver P; Hitti, Rebekkah J; Pettitt, Louise; Jenkins, Christopher A; O'Brien, Dennis P; Shelton, G Diane; De Risio, Luisa; Quintana, Rodrigo Gutierrez; Beltran, Elsa; Mellersh, Cathryn

    2016-09-08

    Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population. Copyright © 2016 Forman et al.

  10. An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed

    Directory of Open Access Journals (Sweden)

    Oliver P. Forman

    2016-09-01

    Full Text Available Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population.

  11. Disruptions in brain networks of older fallers are associated with subsequent cognitive decline: a 12-month prospective exploratory study.

    Directory of Open Access Journals (Sweden)

    Chun Liang Hsu

    Full Text Available Cognitive impairment and impaired mobility are major public health concerns. There is growing recognition that impaired mobility is an early biomarker of cognitive impairment and dementia. The neural basis for this association is currently unclear. We propose disrupted functional connectivity as a potential mechanism. In this 12-month prospective exploratory study, we compared functional connectivity of four brain networks- the default mode network (DMN, fronto-executive network (FEN, fronto-parietal network (FPN, and the primary motor sensory network (SMN--between community-dwelling older adults with ≥ two falls in the last 12 months and their non-falling counterparts (≤ one fall in the last 12 months. Functional connectivity was examined both at rest and during a simple motor tapping task. Compared with non-fallers, fallers showed more connectivity between the DMN and FPN during right finger tapping (p  = 0.04, and significantly less functional connectivity between the SMN and FPN during rest (p ≤ 0.05. Less connectivity between the SMN and FPN during rest was significantly associated with greater decline in both cognitive function and mobility over the12-month period (r =  -0.32 and 0.33 respectively; p ≤ 0.04. Thus, a recent history of multiple falls among older adults without a diagnosis of dementia may indicate sub-clinical changes in brain function and increased risk for subsequent decline.

  12. Disruptions in brain networks of older fallers are associated with subsequent cognitive decline: a 12-month prospective exploratory study.

    Science.gov (United States)

    Hsu, Chun Liang; Voss, Michelle W; Handy, Todd C; Davis, Jennifer C; Nagamatsu, Lindsay S; Chan, Alison; Bolandzadeh, Niousha; Liu-Ambrose, Teresa

    2014-01-01

    Cognitive impairment and impaired mobility are major public health concerns. There is growing recognition that impaired mobility is an early biomarker of cognitive impairment and dementia. The neural basis for this association is currently unclear. We propose disrupted functional connectivity as a potential mechanism. In this 12-month prospective exploratory study, we compared functional connectivity of four brain networks- the default mode network (DMN), fronto-executive network (FEN), fronto-parietal network (FPN), and the primary motor sensory network (SMN)--between community-dwelling older adults with ≥ two falls in the last 12 months and their non-falling counterparts (≤ one fall in the last 12 months). Functional connectivity was examined both at rest and during a simple motor tapping task. Compared with non-fallers, fallers showed more connectivity between the DMN and FPN during right finger tapping (p  = 0.04), and significantly less functional connectivity between the SMN and FPN during rest (p ≤ 0.05). Less connectivity between the SMN and FPN during rest was significantly associated with greater decline in both cognitive function and mobility over the12-month period (r =  -0.32 and 0.33 respectively; p ≤ 0.04). Thus, a recent history of multiple falls among older adults without a diagnosis of dementia may indicate sub-clinical changes in brain function and increased risk for subsequent decline.

  13. Disruption of bradycardia associated with discriminative conditioning in combat veterans with PTSD

    Directory of Open Access Journals (Sweden)

    Jay P Ginsberg

    2008-06-01

    Full Text Available Jay P Ginsberg1,2, Edwin Ayers3, Louisa Burriss1, Donald A Powell1,41Shirley L. Buchanan Neuroscience Laboratory, Dorn VA Medical Center, Columbia, SC, USA; 2Department of Pharmacology, Physiology, and Neuroscience, School of Medicine, 4Department of Psychology, University of South Carolina, Columbia, SC, USA; 3Department of Psychology, South Carolina State University, Orangeburg, SC, USAAbstract: The effects of combat-related posttraumatic stress disorder (PTSD on heart rate (HR responding associated with a discriminative delay eyeblink (EB conditioning paradigm are reported. Combat PTSD+, Combat PTSD−, and Noncombat PTSD− veterans were assessed with psychometric self-report measures, and baseline heart rate variability (HRV was measured before receiving a 72-trial session of discriminative EB classical conditioning. Two types (red or green light of conditioned stimuli (CS were used: one (CS+ predicted a tone, followed immediately by an aversive stimulus (corneal airpuff; the other (CS− predicted a tone alone, not followed by the airpuff. The light signal was presented for 5 seconds, during which HR was measured. On all psychometric measures, the PTSD+ subgroup was significantly different from the PTSD− subgroups (Combat + Noncombat, and the PTSD− subgroups did not significantly differ from each other. A linear deceleration in HR to CS+ and CS− signals was found in the combined PTSD− subgroup and on CS− trials in the PTSD+ subgroup, but was not present on CS+ trials in the PTSD+ subgroup. Results are interpreted with respect to a behavioral stages model of conditioned bradycardia and in terms of neural substrates which are both critical to HR conditioning and known to be abnormal in PTSD.Keywords: bradycardia, PTSD, combat veterans, classical conditioning

  14. Amyloid Associated Intermittent Network Disruptions in Cognitively Intact Older Subjects: Structural Connectivity Matters

    Directory of Open Access Journals (Sweden)

    Susanne G. Mueller

    2017-12-01

    Full Text Available Observations in animal models suggest that amyloid can cause network hypersynchrony in the early preclinical phase of Alzheimer's disease (AD. The aim of this study was (a to obtain evidence of paroxysmal hypersynchrony in cognitively intact subjects (CN with increased brain amyloid load from task-free fMRI exams using a dynamic analysis approach, (b to investigate if and how hypersynchrony interferes with memory performance, and (c to describe its relationship with gray and white matter connectivity. Florbetapir-F18 PET and task-free 3T functional and structural MRI were acquired in 47 CN (age = 70.6 ± 6.6, 17 were amyloid pos (florbetapir SUVR >1.11. A parcellation scheme encompassing 382 regions of interest was used to extract regional gray matter volumes, FA-weighted fiber tracts and regional BOLD signals. Graph analysis was used to characterize the gray matter atrophy profile and the white matter connectivity of each subject. The fMRI data was processed using a combination of sliding windows, graph and hierarchical cluster analysis. Each activity cluster was characterized by identifying strength dispersion (difference between pos and neg strength their maximal and minimal pos and neg strength rois and by investigating their distribution and association with memory performance and gray and white matter connectivity using spearman rank correlations (FDR p < 0.05. The cluster analysis identified eight different activity clusters. Cluster 8 was characterized by the largest strength dispersion indicating hypersynchrony. Its duration/subject was positively correlated with amyloid load (r = 0.42, p = 0.03 and negatively with memory performance (CVLT delayed recall r = −0.39 p = 0.04. The assessment of the regional strength distribution indicated a functional disconnection between mesial temporal structures and the rest of the brain. White matter connectivity was increased in left lateral and mesial temporal lobe and was positively correlated

  15. The association between Disruptive Mood Dysregulation Disorder symptoms and sleep problems in children with and without ADHD.

    Science.gov (United States)

    Waxmonsky, James G; Mayes, Susan D; Calhoun, Susan L; Fernandez-Mendoza, Julio; Waschbusch, Daniel A; Bendixsen, Brianna H; Bixler, Edward O

    2017-09-01

    Many youth experience persistent irritability and recurrent temper outbursts, conceptualized by DSM-5 as Disruptive Mood Dysregulation Disorder (DMDD). Sleep deprivation impairs emotion regulation which could increase rates of DMDD symptoms, especially in those with preexisting regulatory impairments, as seen with ADHD. However, there has been little examination of the relationship between chronic sleep problems and DMDD symptoms. Associations between DMDD symptoms and sleep parameters in children were assessed using parent-report and objective measures of sleep in a general population sample (N = 665) and an ADHD sample (N = 784). Irritability, temper outbursts, sleep problems and other psychological problems were assessed with the Pediatric Behavior Scale. The general population study also completed overnight polysomnography (PSG). DMDD symptoms were reported in 9.2% of the community sample and 31.4% of the ADHD sample. In both samples, children with DMDD symptoms had significantly higher parent-reported sleep problems than children without DMDD symptoms. Children with sleep problems had significantly higher DMDD scores than children without sleep problems. However, DMDD symptoms were most strongly associated with oppositional behavior. Sleep problems were not a significant contributor. Hyperactivity-impulsivity was most strongly associated with sleep problems, and DMDD was not a significant contributor. Children with and without DMDD symptoms did not differ significantly on any PSG parameter. Associations between parent-reported sleep problems and DMDD symptoms were due to their shared relationship with other behavioral problems. Therefore, chronic sleep problems do not appear to be a primary source of DMDD symptoms in children with or without ADHD. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Wound Disruption Following Colorectal Operations.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

    2015-12-01

    Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

  17. Candidate genes and single nucleotide polymorphisms associated with variation in residual feed intake in beef cattle.

    Science.gov (United States)

    Karisa, B K; Thomson, J; Wang, Z; Stothard, P; Moore, S S; Plastow, G S

    2013-08-01

    The candidate gene approach was used to identify genes associated with residual feed intake (RFI) in beef steers. The approach uses prior knowledge of gene functions to predict their biological role in the variation observed in a trait. It is suited to identify genes associated with complex traits where each gene has a relatively small effect. First, positional candidate genes were identified within the genomic positions of previously reported QTL associated with component traits related to RFI such as dry matter intake (DMI), growth, feed conversion ratio (FCR), average daily gain (ADG), and energy balance. Secondly, the positional candidate genes were prioritized into functional candidate genes according to their biological functions and their relationship with the biological processes associated with RFI including carbohydrate, fat and protein metabolism, thermoregulation, immunity and muscle activity. Single nucleotide polymorphisms (SNPs) located within the functional candidate genes were identified using mRNA sequences and prioritized into functional classes such as non-synonymous (nsSNP), synonymous (sSNP) or intronic SNP. A total of 117 nsSNP were considered as functional SNP and genotyped in steers at the University of Alberta ranch in Kinsella. Multiple marker association analysis in ASReml was performed using RFI data obtained from 531 beef steers. Twenty-five SNP were significantly associated with RFI (P < 0.05) accounting for 19.7% of the phenotypic variation. Using SIFT program to predict the effect of the SNP on the function of the corresponding protein, 3 of the 25 SNP were predicted to cause a significant effect on protein function (P < 0.05). One of the 3 SNP was located in the GHR gene and was also associated with a significant effect on the tertiary structure of the GHR protein (P < 0.05) as modeled using SWISSModel software. Least square means for each genotype were estimated and an over-dominance effect was observed for the SNP located in the

  18. Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance.

    Science.gov (United States)

    Shinjo, Satoko; Jiang, Shuying; Nameta, Masaaki; Suzuki, Tomohiro; Kanai, Mai; Nomura, Yuta; Goda, Nobuhito

    2017-10-01

    The mitochondria-associated ER membrane (MAM) is a specialized subdomain of ER that physically connects with mitochondria. Although disruption of inter-organellar crosstalk via the MAM impairs cellular homeostasis, its pathological significance in insulin resistance in type 2 diabetes mellitus remains unclear. Here, we reveal the importance of reduced MAM formation in the induction of fatty acid-evoked insulin resistance in hepatocytes. Palmitic acid (PA) repressed insulin-stimulated Akt phosphorylation in HepG2 cells within 12h. Treatment with an inhibitor of the ER stress response failed to restore PA-mediated suppression of Akt activation. Mitochondrial reactive oxygen species (ROS) production did not increase in PA-treated cells. Even short-term exposure (3h) to PA reduced the calcium flux from ER to mitochondria, followed by a significant decrease in MAM contact area, suggesting that PA suppressed the functional interaction between ER and mitochondria. Forced expression of mitofusin-2, a critical component of the MAM, partially restored MAM contact area and ameliorated the PA-elicited suppression of insulin sensitivity with Ser473 phosphorylation of Akt selectively improved. These results suggest that loss of proximity between ER and mitochondria, but not perturbation of homeostasis in the two organelles individually, plays crucial roles in PA-evoked Akt inactivation in hepatic insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Association between occlusal force distribution in implant overdenture prostheses and residual ridge resorption.

    Science.gov (United States)

    Khuder, T; Yunus, N; Sulaiman, E; Ibrahim, N; Khalid, T; Masood, M

    2017-05-01

    This study aimed to investigate residual ridge resorption (RRR) of anterior and posterior maxillary and mandibular edentulous ridges, in patients treated with mandibular implant overdentures (IOD) and compare with conventional complete denture (CD) wearers, and to determine at each location, the association of RRR with the occlusal forces distribution and other patients' variables. The anterior and posterior RRR of IOD (six males, 17 females) and CD (12 males, 11 females) groups were determined using baseline and follow-up dental panaromic radiographs (DPT) (mean intervals 4 ± 1·8 years). The bone ratios were calculated using proportional area: anatomic to fixed reference areas and mean difference of ratios between the intervals determined RRR. The ridge locations included anterior and posterior maxillary and posterior mandibular arches. The T-Scan III digital occlusal system was used to record anterior and posterior percentage occlusal force (%OF) distributions. There were significant differences in anterior and posterior %OF between treatment groups. Two-way anova showed RRR was significant for arch locations (P = 0·005), treatment group (IOD versus CD) (P = 0·001), however, no significant interaction (P = 0·799). Multivariate regression analyses showed significant association between RRR and %OF at anterior maxilla (P = 0·000) and posterior mandible (P = 0·023) and for treatment groups at posterior maxilla (P = 0·033) and mandibular areas (P = 0·021). Resorption was observed in IOD compared to CD groups, with 8·5% chance of less resorption in former and 7·8% in the latter location. Depending on arch location, ridge resorption at various locations was associated with occlusal force distribution and/or treatment groups (implant prostheses or conventional complete dentures). © 2017 John Wiley & Sons Ltd.

  20. Digital Disruption

    DEFF Research Database (Denmark)

    Rosenstand, Claus Andreas Foss

    Disruption var frem til slutningen af 2016 i Danmark et ord, som kun få kendte og endnu færre havde en holdning til. Nu er der imidlertid sat fokus på begrebet fra allerhøjeste nationale sted, idet regeringen har taget initiativ til nedsættelse af det, Statsminister Lars Løkke Rasmussen indtil...... videre kalder et ”disruption-råd”. Faktisk er rådet skrevet ind i 2016 regeringsgrundlaget for VLK-regeringen. Disruption af organisationer er ikke et nyt fænomen; men hastigheden, hvormed det sker, er stadig accelererende. Årsagen er den globale mega-trend: Digitalisering. Og derfor er specielt digital...... disruption en sag for os alle. Derfor er det også for vigtigt et emne til, at det udelukkende behandles i elitære videnskabelige, industrielle og politiske kredse. Der er behov for en bredere samfundsdebat; og bogen er et forskningsbaseret bidrag ind i denne debat. For a kvalificere debatten om disruption i...

  1. Intimate partner violence against low-income women in Mexico City and associations with work-related disruptions: a latent class analysis using cross-sectional data.

    Science.gov (United States)

    Gupta, Jhumka; Willie, Tiara C; Harris, Courtney; Campos, Paola Abril; Falb, Kathryn L; Garcia Moreno, Claudia; Diaz Olavarrieta, Claudia; Okechukwu, Cassandra A

    2018-03-07

    Disrupting women's employment is a strategy that abusive partners could use to prevent women from maintaining economic independence and stability. Yet, few studies have investigated disruptions in employment among victims of intimate partner violence (IPV) in low-income and middle-income countries. Moreover, even fewer have sought to identify which female victims of IPV are most vulnerable to such disruptions. Using baseline data from 947 women in Mexico City enrolled in a randomised controlled trial, multilevel latent class analysis (LCA) was used to classify women based on their reported IPV experiences. Furthermore, multilevel logistic regression analyses were performed on a subsample of women reporting current work (n=572) to investigate associations between LCA membership and IPV-related employment disruptions. Overall, 40.6% of women who were working at the time of the survey reported some form of work-related disruption due to IPV. LCA identified four distinct classes of IPV experiences: Low Physical and Sexual Violence (39.1%); High Sexual and Low Physical Violence class (9.6%); High Physical and Low Sexual Violence and Injuries (36.5%); High Physical and Sexual Violence and Injuries (14.8%). Compared with women in the Low Physical and Sexual Violence class, women in the High Physical and Sexual Violence and Injuries class and women in the High Physical and Low Sexual Violence and Injuries class were at greater risk of work disruption (adjusted relative risk (ARR) 2.44, 95% CI 1.80 to 3.29; ARR 2.05, 95% CI 1.56 to 2.70, respectively). No other statistically significant associations emerged. IPV, and specific patterns of IPV experiences, must be considered both in work settings and, more broadly, by economic development programmes. NCT01661504. © 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.

  2. Harsh Parenting As a Potential Mediator of the Association Between Intimate Partner Violence and Child Disruptive Behavior in Families With Young Children

    Science.gov (United States)

    Grasso, Damion J.; Henry, David; Kestler, Jacqueline; Nieto, Ricardo; Wakschlag, Lauren S.; Briggs-Gowan, Margaret J.

    2015-01-01

    Young children living with intimate partner violence (IPV) are often also exposed to harsh parenting. Both forms of violence increase children’s risk for clinically significant disruptive behavior, which can place them on a developmental trajectory associated with serious psychological impairment later in life. Although it is hypothesized that IPV behaviors may spillover into harsh parenting, and thereby influence risk for disruptive behavior, relatively little is known about these processes in families with young children. The current study examines the overlap of the quality and frequency of psychological and physical forms of IPV and harsh parenting, and tests whether harsh parenting mediates the relationship between IPV and child disruptive behavior in a diverse cross-sectional sample of 81 children ages 4 to 6 years. Results suggest that mothers reporting a greater occurrence of psychologically aggressive IPV (e.g., yelling, name-calling) more often engage in psychological and physical aggression toward their children (odds ratios [ORs] = 4.6–9.9). Mothers reporting a greater occurrence of IPV in the form of physical assault more often engage in mild to more severe forms of physical punishment with potential harm to the child (ORs = 3.8–5.0). Psychological and physical forms of IPV and harsh parenting all significantly correlated with maternal reports of child disruptive behavior (r = .29–.40). Psychological harsh parenting partially mediated the association between psychological IPV and child disruptive behavior. However, a significant direct effect of psychological IPV on preschool children’s disruptive behavior remained. Implications for child welfare policy and practice and intervention, including the need for increased awareness of the negative impact of psychological IPV on young children, are discussed. PMID:25724875

  3. Harsh Parenting As a Potential Mediator of the Association Between Intimate Partner Violence and Child Disruptive Behavior in Families With Young Children.

    Science.gov (United States)

    Grasso, Damion J; Henry, David; Kestler, Jacqueline; Nieto, Ricardo; Wakschlag, Lauren S; Briggs-Gowan, Margaret J

    2016-07-01

    Young children living with intimate partner violence (IPV) are often also exposed to harsh parenting. Both forms of violence increase children's risk for clinically significant disruptive behavior, which can place them on a developmental trajectory associated with serious psychological impairment later in life. Although it is hypothesized that IPV behaviors may spillover into harsh parenting, and thereby influence risk for disruptive behavior, relatively little is known about these processes in families with young children. The current study examines the overlap of the quality and frequency of psychological and physical forms of IPV and harsh parenting, and tests whether harsh parenting mediates the relationship between IPV and child disruptive behavior in a diverse cross-sectional sample of 81 children ages 4 to 6 years. Results suggest that mothers reporting a greater occurrence of psychologically aggressive IPV (e.g., yelling, name-calling) more often engage in psychological and physical aggression toward their children (odds ratios [ORs] = 4.6-9.9). Mothers reporting a greater occurrence of IPV in the form of physical assault more often engage in mild to more severe forms of physical punishment with potential harm to the child (ORs = 3.8-5.0). Psychological and physical forms of IPV and harsh parenting all significantly correlated with maternal reports of child disruptive behavior (r = .29-.40). Psychological harsh parenting partially mediated the association between psychological IPV and child disruptive behavior. However, a significant direct effect of psychological IPV on preschool children's disruptive behavior remained. Implications for child welfare policy and practice and intervention, including the need for increased awareness of the negative impact of psychological IPV on young children, are discussed. © The Author(s) 2015.

  4. Longitudinal Associations Between Preschool Disruptive Mood Dysregulation Disorder Symptoms and Neural Reactivity to Monetary Reward During Preadolescence

    Science.gov (United States)

    Dougherty, Lea R.; Kujawa, Autumn; Hajcak, Greg; Carlson, Gabrielle A.; Klein, Daniel N.

    2016-01-01

    Abstract Objective: Reward-processing abnormalities are thought to be a key feature of various psychiatric disorders and may also play a role in disruptive mood dysregulation disorder (DMDD), a new diagnosis in DSM-5. In the current study, we used event-related potentials (ERP) sensitive to monetary gains (i.e., the reward positivity [RewP]) and losses (i.e., the N200) to examine associations between symptoms of DMDD during early childhood and later reward processing during preadolescence. Methods: To assess early emerging DMDD symptoms in a large longitudinal community sample (n=373) of 3-year old children, we administered a diagnostic interview, Preschool Age Psychiatric Assessment (PAPA) with parents. At a later assessment, ∼6 years later, children completed a monetary reward task while an electroencephalogram (EEG) was recorded. Children's lifetime history of psychopathology was also assessed at that time using Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with the child and parent. Results: Multiple regression analyses revealed that age 3 DMDD symptoms predicted an enhanced RewP to monetary rewards in preadolescence. This association is independent of demographics and lifetime history of symptoms of depression, any anxiety disorder, attention-deficit disorder, oppositional defiant disorder, or conduct disorder Conclusions: Early manifestations of DMDD in children as young as 3 years old predicted enhanced reward processing later in development. These findings add to the growing corpus of literature on the pathophysiology of DMDD, and underscore the predictive validity of preschool DMDD on a neural level. PMID:26771832

  5. Bayesian classification of residues associated with protein functional divergence: Arf and Arf-like GTPases

    Directory of Open Access Journals (Sweden)

    Neuwald Andrew F

    2010-12-01

    Full Text Available Abstract Background Certain residues within proteins are highly conserved across very distantly related organisms, yet their (presumably critical structural or mechanistic roles are completely unknown. To obtain clues regarding such residues within Arf and Arf-like (Arf/Arl GTPases--which function as on/off switches regulating vesicle trafficking, phospholipid metabolism and cytoskeletal remodeling--I apply a new sampling procedure for comparative sequence analysis, termed multiple category Bayesian Partitioning with Pattern Selection (mcBPPS. Results The mcBPPS sampler classified sequences within the entire P-loop GTPase class into multiple categories by identifying those evolutionarily-divergent residues most likely to be responsible for functional specialization. Here I focus on categories of residues that most distinguish various Arf/Arl GTPases from other GTPases. This identified residues whose specific roles have been previously proposed (and in some cases corroborated experimentally and that thus serve as positive controls, as well as several categories of co-conserved residues whose possible roles are first hinted at here. For example, Arf/Arl/Sar GTPases are most distinguished from other GTPases by a conserved aspartate residue within the phosphate binding loop (P-loop and by co-conserved residues nearby that, together, can form a network of salt-bridge and hydrogen bond interactions centered on the GTPase active site. Residues corresponding to an N-[VI] motif that is conserved within Arf/Arl GTPases may play a role in the interswitch toggle characteristic of the Arf family, whereas other, co-conserved residues may modulate the flexibility of the guanine binding loop. Arl8 GTPases conserve residues that strikingly diverge from those typically found in other Arf/Arl GTPases and that form structural interactions suggestive of a novel interswitch toggle mechanism. Conclusions This analysis suggests specific mutagenesis experiments to

  6. Politisk disruption

    DEFF Research Database (Denmark)

    Tække, Jesper

    2018-01-01

    Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på.......Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på....

  7. Disrupting Business

    DEFF Research Database (Denmark)

    Cox, Geoff; Bazzichelli, Tatiana

    Disruptive Business explores some of the interconnections between art, activism and the business concept of disruptive innovation. With a backdrop of the crisis of financial capitalism, austerity cuts in the cultural sphere, the idea is to focus on potential art strategies in relation to a broken...... economy. In a perverse way, we ask whether this presents new opportunities for cultural producers to achieve more autonomy over their production process. If it is indeed possible, or desirable, what alternative business models emerge? The book is concerned broadly with business as material for reinvention...

  8. Complete nucleotide sequence of Bacillus subtilis (natto) bacteriophage PM1, a phage associated with disruption of food production.

    Science.gov (United States)

    Umene, Kenichi; Shiraishi, Atsushi

    2013-06-01

    "Natto", considered a traditional food, is made by fermenting boiled soybeans with Bacillus subtilis (natto), which is a natto-producing strain related to B. subtilis. The production of natto is disrupted by phage infections of B. subtilis (natto); hence, it is necessary to control phage infections. PM1, a phage of B. subtilis (natto), was isolated during interrupted natto production in a factory. In a previous study, PM1 was classified morphologically into the family Siphoviridae, and its genome, comprising approximately 50 kbp of linear double-stranded DNA, was assumed to be circularly permuted. In the present study, the complete nucleotide sequence of the PM1 genomic DNA of 50,861 bp (41.3 %G+C) was determined, and 86 open reading frames (ORFs) were deduced. Forty-one ORFs of PM1 shared similarities with proteins deduced from the genome of phages reported so far. Twenty-three ORFs of PM1 were associated with functions related to the phage multiplication process of gene control, DNA replication/modification, DNA packaging, morphogenesis, and cell lysis. Bacillus subtilis (natto) produces a capsular polypeptide of glutamate with a γ-linkage (called poly-γ-glutamate), which appears to serve as a physical barrier to phage adsorption. One ORF of PM1 had similarity with a poly-γ-glutamate hydrolase, which is assumed to degrade the capsular barrier to allow phage progenies to infect encapsulated host cells. The genome analysis of PM1 revealed the characteristics of the phage that are consistent as Bacillus subtilis (natto)-infecting phage.

  9. Mutations in USP9X Are Associated with X-Linked Intellectual Disability and Disrupt Neuronal Cell Migration and Growth

    Science.gov (United States)

    Homan, Claire C.; Kumar, Raman; Nguyen, Lam Son; Haan, Eric; Raymond, F. Lucy; Abidi, Fatima; Raynaud, Martine; Schwartz, Charles E.; Wood, Stephen A.; Gecz, Jozef; Jolly, Lachlan A.

    2014-01-01

    With a wealth of disease-associated DNA variants being recently reported, the challenges of providing their functional characterization are mounting. Previously, as part of a large systematic resequencing of the X chromosome in 208 unrelated families with nonsyndromic X-linked intellectual disability, we identified three unique variants (two missense and one protein truncating) in USP9X. To assess the functional significance of these variants, we took advantage of the Usp9x knockout mouse we generated. Loss of Usp9x causes reduction in both axonal growth and neuronal cell migration. Although overexpression of wild-type human USP9X rescued these defects, all three USP9X variants failed to rescue axonal growth, caused reduced USP9X protein localization in axonal growth cones, and (in 2/3 variants) failed to rescue neuronal cell migration. Interestingly, in one of these families, the proband was subsequently identified to have a microdeletion encompassing ARID1B, a known ID gene. Given our findings it is plausible that loss of function of both genes contributes to the individual's phenotype. This case highlights the complexity of the interpretations of genetic findings from genome-wide investigations. We also performed proteomics analysis of neurons from both the wild-type and Usp9x knockout embryos and identified disruption of the cytoskeleton as the main underlying consequence of the loss of Usp9x. Detailed clinical assessment of all three families with USP9X variants identified hypotonia and behavioral and morphological defects as common features in addition to ID. Together our data support involvement of all three USP9X variants in ID in these families and provide likely cellular and molecular mechanisms involved. PMID:24607389

  10. Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

    Science.gov (United States)

    Bellanger, Martine; Demeneix, Barbara; Grandjean, Philippe; Zoeller, R Thomas; Trasande, Leonardo

    2015-04-01

    Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients and Participants, and Intervention: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. The panel identified a 70-100% probability that polybrominated diphenyl ether and organophosphate exposures contribute to IQ loss in the European population. Polybrominated diphenyl ether exposures were associated with 873,000 (sensitivity analysis, 148,000 to 2.02 million) lost IQ points and 3290 (sensitivity analysis, 3290 to 8080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis, €1.58 billion to €22.4 billion). Organophosphate exposures were associated with 13.0 million (sensitivity analysis, 4.24 million to 17.1 million) lost IQ points and 59 300 (sensitivity analysis, 16,500 to 84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis, €46.8 billion to €194 billion). Autism spectrum disorder causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis, 126-631) attributable cases at a cost of €199 million

  11. Increased residual force enhancement in older adults is associated with a maintenance of eccentric strength.

    Directory of Open Access Journals (Sweden)

    Geoffrey A Power

    Full Text Available Despite an age-related loss of voluntary isometric and concentric strength, muscle strength is well maintained during lengthening muscle actions (i.e., eccentric strength in old age. Additionally, in younger adults during lengthening of an activated skeletal muscle, the force level observed following the stretch is greater than the isometric force at the same muscle length. This feature is termed residual force enhancement (RFE and is believed to be a combination of active and passive components of the contractile apparatus. The purpose of this study was to provide an initial assessment of RFE in older adults and utilize aging as a muscle model to explore RFE in a system in which isometric force production is compromised, but structural mechanisms of eccentric strength are well-maintained. Therefore, we hypothesised that older adults will experience greater RFE compared with young adults. Following a reference maximal voluntary isometric contraction (MVC of the dorsiflexors in 10 young (26.1 ± 2.7 y and 10 old (76.0 ± 6.5 y men, an active stretch was performed at 15°/s over a 30° ankle joint excursion ending at the same muscle length as the reference MVCs (40° of plantar flexion. Any additional torque compared with the reference MVC therefore represented RFE. In older men RFE was ~2.5 times greater compared to young. The passive component of force enhancement contributed ~37% and ~20% to total force enhancement, in old and young respectively. The positive association (R(2 = 0.57 between maintained eccentric strength in old age and RFE indicates age-related mechanisms responsible for the maintenance of eccentric strength likely contributed to the observed elevated RFE. Additionally, as indicated by the greater passive force enhancement, these mechanisms may be related to increased muscle series elastic stiffness in old age.

  12. Crop residue management and fertilization effects on soil organic matter and associated biological properties.

    Science.gov (United States)

    Zhao, Bingzi; Zhang, Jiabao; Yu, Yueyue; Karlen, Douglas L; Hao, Xiying

    2016-09-01

    Returning crop residue may result in nutrient reduction in soil in the first few years. A two-year field experiment was conducted to assess whether this negative effect is alleviated by improved crop residue management (CRM). Nine treatments (3 CRM and 3 N fertilizer rates) were used. The CRM treatments were (1) R0: 100 % of the N using mineral fertilizer with no crop residues return; (2) R: crop residue plus mineral fertilizer as for the R0; and (3) Rc: crop residue plus 83 % of the N using mineral and 17 % manure fertilizer. Each CRM received N fertilizer rates at 270, 360, and 450 kg N ha(-1) year(-1). At the end of the experiment, soil NO3-N was reduced by 33 % from the R relative to the R0 treatment, while the Rc treatment resulted in a 21 to 44 % increase in occluded particulate organic C and N, and 80 °C extracted dissolved organic N, 19 to 32 % increase in microbial biomass C and protease activity, and higher monounsaturated phospholipid fatty acid (PLFA):saturated PLFA ratio from stimulating growth of indigenous bacteria when compared with the R treatment. Principal component analysis showed that the Biolog and PLFA profiles in the three CRM treatments were different from each other. Overall, these properties were not influenced by the used N fertilizer rates. Our results indicated that application of 17 % of the total N using manure in a field with crop residues return was effective for improving potential plant N availability and labile soil organic matter, primarily due to a shift in the dominant microorganisms.

  13. MRI findings associated with microscopic residual tumor following unplanned excision of soft tissue sarcomas in the extremities

    International Nuclear Information System (INIS)

    Wang, Lee; Chelala, Lydia; Jose, Jean; Subhawong, Ty K.; Pretell-Mazzini, Juan; Kerr, Darcy A.; Yang, Xuan

    2018-01-01

    MRI is often used to determine the presence of residual disease following unplanned excisions (UPE) of soft tissue sarcomas (STS). We sought to identify MRI features associated with histologic evidence of residual disease after TBE. This was an IRB-approved retrospective review of 27 patients with R1-type UPE of STS over a 32-month period, with subsequent MRI and TBE. MRI studies were retrospectively evaluated to determine depth of tissue involvement, presence of nodular enhancement, and maximum length of soft tissue edema normalized to extremity size. MRI findings were correlated with histology from unplanned excision and TBE. Among the 21 subjects, there were 13 males and 8 females, mean age 58. Eighteen of 21 STS were grade 2 or 3. Deep compartments were involved in 5/21 cases. Original margins were positive in 17/21 UPE, with inadequate margin assessment in the remaining 4 cases. Residual tumor was present at TBE in 11/21 cases; it was found in 4/6 cases with nodular enhancement and 7/15 cases without nodular enhancement (sensitivity = 0.36; specificity = 0.80; PPV = 0.67; NPV = 0.53). Increased extent of soft tissue edema increased the likelihood of residual tumor at TBE (OR = 35.0; 95% CI = 1.6 to 752.7; p = 0.023). Nodular enhancement is neither sensitive nor specific in predicting residual microscopic tumor in TBE following UPE. Extensive soft tissue edema on MRI after UPE increases the likelihood of finding a residual microscopic tumor, justifying ample margins at TBE and consideration of adjuvant therapy. (orig.)

  14. Travel-Associated Rabies in Pets and Residual Rabies Risk, Western Europe.

    Science.gov (United States)

    Ribadeau-Dumas, Florence; Cliquet, Florence; Gautret, Philippe; Robardet, Emmanuelle; Le Pen, Claude; Bourhy, Hervé

    2016-07-01

    In 2015, countries in western Europe were declared free of rabies in nonflying mammals. Surveillance data for 2001-2013 indicate that risk for residual rabies is not 0 because of pet importation from countries with enzootic rabies. However, the risk is so low (7.52 × 10(-10)) that it probably can be considered negligible.

  15. Minimal residual disease after surgery of HPV 16-associated tumours as target for immunotherapy

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Reiniš, Milan; Šímová, Jana

    2006-01-01

    Roč. 18, Supplement 1 (2006), - ISSN 1107-3756. [World Congress on Advances in Oncology /11./ and International Symposium on Molecular Medicine /9./. 12.10.2006-14.10.2006, Hersonissos] R&D Projects: GA MZd(CZ) NR7807; GA ČR(CZ) GA301/04/0492; GA AV ČR(CZ) IAA500520605 Institutional research plan: CEZ:AV0Z50520514 Keywords : minimal residual disease * HPV16 * immunotherapy Subject RIV: EB - Genetics ; Molecular Biology

  16. Depletion of Treg cells inhibits minimal residual disease after surgery of HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Šímová, Jana; Bubeník, Jan; Bieblová, Jana; Rosalia, Rodney Alexander; Frič, Jan; Reiniš, Milan

    2006-01-01

    Roč. 29, č. 6 (2006), s. 1567-1571 ISSN 1019-6439 R&D Projects: GA ČR(CZ) GA301/04/0492 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Liga proti rakovině(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * residual tumour disease * Treg cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.556, year: 2006

  17. HPV16-associated tumours: Therapy of surgical minimal residual disease with dendritic cell-based vaccines

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Indrová, Marie; Mendoza, Luis; Mikyšková, Romana; Bieblová, Jana; Bubeník, Jan; Šímová, Jana

    2004-01-01

    Roč. 25, č. 4 (2004), s. 1165-1170 ISSN 1019-6439 R&D Projects: GA MZd NC7148; GA ČR GA301/04/0492; GA ČR GA301/01/0985; GA AV ČR IAA5052203 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV 16 * minimal residual tumour disease * dendritic cells Subject RIV: EC - Immunology Impact factor: 3.056, year: 2004

  18. Quantification of Lincomycin Resistance Genes Associated with Lincomycin Residues in Waters and Soils Adjacent to Representative Swine Farms in China

    Directory of Open Access Journals (Sweden)

    Liang eLi

    2013-12-01

    Full Text Available Lincomycin is commonly used on swine farms for growth promotion as well as disease treatment and control. Consequently, lincomycin may accumulate in the environment adjacent to the swine farms in many ways, thereby influencing antibiotic resistance in the environment. Levels of lincomycin-resistance genes and lincomycin residues in water and soil samples collected from multiple sites near wastewater discharge areas were investigated in this study. Sixteen lincomycin-resistance and 16S rRNA genes were detected using real-time PCR. Three genes, lnu(F, erm(A and erm(B, were detected in all water and soil samples except control samples. Lincomycin residues were determined by rapid resolution liquid chromatography-tandem mass spectrometry, with concentrations detected as high as 9.29 ng/mL in water and 0.97 ng/g in soil. A gradual reduction in the levels of lincomycin-resistance genes and lincomycin residues in the waters and soils were detected from multiple sites along the path of wastewater discharging to the surrounding environment from the swine farms. Significant correlations were found between levels of lincomycin-resistance genes in paired water and soil samples (r = 0.885, p = 0.019, and between lincomycin-resistance genes and lincomycin residues (r = 0.975, p < 0.01. This study emphasized the potential risk of dissemination of lincomycin-resistance genes such as lnu(F, erm(A and erm(B, associated with lincomycin residues in surrounding environments adjacent to swine farms.

  19. ADHD and Disruptive behavior scores – associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents

    Directory of Open Access Journals (Sweden)

    Larsson Jan-Olov

    2008-04-01

    Full Text Available Abstract Background Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD and Disruptive Behavior Disorder (DBD. We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B (MAO-B activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats (MAO-A VNTR and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region (5-HTT LPR. Methods A population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL. Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5-HTT genes. Results We found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder (ODD. In girls, there was also an association between the heterozygote long/short 5-HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5-HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder (CD. In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior. Conclusion Our study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.

  20. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...

  1. Disrupted Disclosure

    DEFF Research Database (Denmark)

    Krause Hansen, Hans; Uldam, Julie

    , and onongoing research in the extractive industries and social movements, this work-in-progress sets outto examine (a) why and how transparency has been constructed and mobilized in recentinternational attempts to regulate the extractive industries, specifically oil and gas companies; (b)how companies’ normal...... appearances become challenged through disruptive disclosures in mediaenvironments characterized by multiple levels of visibility, with companies both observing andbeing observed by civil society groups that criticize them; (c) why and how the mobilization aroundtransparency and ensuing practices......While projects of governance by transparency have become widespread over the past decades, theyare usually investigated and theorized in isolation from the wider field of visibility and surveillancein which they are embedded. Building on theories of governance, visibility and surveillance...

  2. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site

    Energy Technology Data Exchange (ETDEWEB)

    Kassotis, Christopher D., E-mail: christopher.kassotis@duke.edu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Iwanowicz, Luke R. [U.S. Geological Survey, Leetown Science Center, Fish Health Branch, 11649 Leetown Road, Kearneysville, WV 25430 (United States); Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam C. [U.S. Geological Survey, National Research Program, 12201 Sunrise Valley Drive, MS 430, Reston, VA 20192 (United States); Orem, William H. [U.S. Geological Survey, Eastern Energy Resources Science Center, 12201 Sunrise Valley Drive, MS 956, Reston, VA 20192 (United States); Nagel, Susan C., E-mail: nagels@health.missouri.edu [Department of Obstetrics, Gynecology and Women' s Health, University of Missouri, Columbia, MO 65211 (United States)

    2016-07-01

    Currently, > 95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby. - Highlights: • Oil and gas wastewater disposal may increase endocrine disrupting activity in water. • Tested EDC activity in surface water near oil and gas wastewater injection site. • Water downstream had significantly

  3. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies

    DEFF Research Database (Denmark)

    Kim, Hyung-Goo; Kim, Hyun-Taek; Leach, Natalia T

    2012-01-01

    development, and suppression of the latter led to both craniofacial abnormalities and neuronal apoptosis. Along with lysine-specific demethylase 1 (LSD1), PHF21A, also known as BHC80, is a component of the BRAF-histone deacetylase complex that represses target-gene transcription. In lymphoblastoid cell lines...... from two translocation subjects in whom PHF21A was directly disrupted by the respective breakpoints, we observed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional...

  4. Residual deposits (residual soil)

    International Nuclear Information System (INIS)

    Khasanov, A.Kh.

    1988-01-01

    Residual soil deposits is accumulation of new formate ore minerals on the earth surface, arise as a result of chemical decomposition of rocks. As is well known, at the hyper genes zone under the influence of different factors (water, carbonic acid, organic acids, oxygen, microorganism activity) passes chemical weathering of rocks. Residual soil deposits forming depends from complex of geologic and climatic factors and also from composition and physical and chemical properties of initial rocks

  5. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site

    Science.gov (United States)

    Kassotis, Christopher D.; Iwanowicz, Luke R.; Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam; Orem, William H.; Nagel, Susan C.

    2016-01-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby.

  6. Aging of aluminum/iron-based drinking water treatment residuals in lake water and their association with phosphorus immobilization capability.

    Science.gov (United States)

    Wang, Changhui; Yuan, Nannan; Pei, Yuansheng; Jiang, He-Long

    2015-08-15

    Aluminum and Fe-based drinking water treatment residuals (DWTRs) have shown a high potential for use by geoengineers in internal P loading control in lakes. In this study, aging of Al/Fe-based DWTRs in lake water under different pH and redox conditions associated with their P immobilization capability was investigated based on a 180-day incubation test. The results showed that the DWTRs before and after incubation under different conditions have similar structures, but their specific surface area and pore volume, especially mesopores with radius at 2.1-5.0 nm drastically decreased. The oxalate extractable Al contents changed little although a small amount of Al transformed from oxidizable to residual forms. The oxalate extractable Fe contents also decreased by a small amount, but the transformation from oxidizable to residual forms were remarkable, approximately by 14.6%. However, the DWTRs before and after incubation had similar P immobilization capabilities in solutions and lake sediments. Even the maximum P adsorption capacity estimated by the Langmuir model increased after incubation. Therefore, it was not necessary to give special attention to the impact of Al and Fe aging on the effectiveness of DWTRs for geoengineering in lakes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Human health risks associated with residual pesticide levels in edible tissues of slaughtered cattle in Benin City, Southern Nigeria

    Directory of Open Access Journals (Sweden)

    Isioma Tongo

    2015-01-01

    Full Text Available Pesticide residues in meat is of growing concern due to possible adverse effects on humans. Pesticide levels were assessed in five edible cattle parts: muscle, liver, kidney and tongue tissues to determine human health risk associated with consumption of these tissues. Health risk estimates were analysed using estimated daily intake (EDI, hazard quotient (HQ and hazard index (HI for two (2 age/weight categories: 1–11years/30 kg for children while 70 kg was used for adult. Risks were categorized for non-carcinogenic and carcinogenic health effects and measured at the average, maximum, 50th and 95th percentiles of the measured exposure concentrations (MEC. Total pesticide residues ranged from 2.38 to 3.86 μg/kg (muscle, 3.58 to 6.3 μg/kg (liver, 1.87 to 4.59 μg/kg (kidney and 2.54 to 4.35 μg/kg (tongue. Residual pesticide concentrations in the tissues were in the order: Liver > Tongue > Muscle > Kidney. The concentrations of all the assessed pesticides observed in the tissues were however lower than the recommended maximum residual limits (MRLs. Human health risk estimations for the children showed EDI values for heptachlor epoxide, aldrin and dieldrin exceeding threshold values. Non-cancer risk posed to children on consumption of contaminated cattle parts showed HQ values for heptachlor epoxide, aldrin, dieldrin and HI values for organochlorines exceeding 1, indicating the possibility of non-carcinogenic health risks to consumers especially children from consumption of cattle meat from the selected abattoirs.

  8. Probing the disparate effects of arginine and lysine residues on antimicrobial peptide/bilayer association.

    Science.gov (United States)

    Rice, A; Wereszczynski, J

    2017-10-01

    Antimicrobial peptides (AMPs) are key components of the innate immune response and represent promising templates for the development of broad-spectrum alternatives to conventional antibiotics. Most AMPs are short, cationic peptides that interact more strongly with negatively charged prokaryotic membranes than net neutral eukaryotic ones. Both AMPs and synthetic analogues with arginine-like side chains are more active against bacteria than those with lysine-like amine groups, though the atomistic mechanism for this increase in potency remains unclear. To examine this, we conducted comparative molecular dynamics simulations of a model negatively-charged membrane system interacting with two mutants of the AMP KR-12: one with lysine residues mutated to arginines (R-KR12) and one with arginine residues mutated to lysine (K-KR12). Simulations show that both partition analogously to the bilayer and display similar preferences for hydrogen bonding with the anionic POPGs. However, R-KR12 binds stronger to the bilayer than K-KR12 and forms significantly more hydrogen bonds, leading to considerably longer interaction times. Additional simulations with methylated R-KR12 and charge-modified K-KR12 mutants show that the extensive interaction seen in the R-KR12 system is partly due to arginine's strong atomic charge distribution, rather than being purely an effect of the greater number of hydrogen bond donors. Finally, free energy simulations reveal that both peptides are disordered in solution but form an amphipathic α-helix when inserted into the bilayer headgroup region. Overall, these results highlight the role of charge and hydrogen bond strength in peptide bilayer insertion, and offer potential insights for designing more potent analogues in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Anti Myelin Oligodendrocyte Glycoprotein associated Immunoglobulin G (AntiMOG-IgG)-associated Neuromyelitis Optica Spectrum Disorder with Persistent Disease Activity and Residual Cognitive Impairment.

    Science.gov (United States)

    Pandit, Lekha; Nakashima, Ichiro; Mustafa, Sharik; Takahashi, Toshiyuki; Kaneko, Kimhiko

    2017-01-01

    Antibodies targeting myelin oligodendrocyte glycoprotein (MOG) have been recently reported in association with idiopathic inflammatory central nervous system disorders. Initially believed to be a benign disorder, anti MOG-IgG was noted to cause steroid responsive recurrent optic neuritis and isolated longitudinally extensive myelitis. However, there is growing evidence that the disease may be predominantly relapsing, often producing severe visual loss and involving regions other than the spinal cord and optic nerve. We report an adolescent male with an aggressive disease course previously undescribed in anti MOG-IgG-associated disease that left him with residual cognitive dysfunction.

  10. stg fimbrial operon from S. Typhi STH2370 contributes to association and cell disruption of epithelial and macrophage-like cells.

    Science.gov (United States)

    Berrocal, Liliana; Fuentes, Juan A; Trombert, A Nicole; Jofré, Matías R; Villagra, Nicolás A; Valenzuela, Luis M; Mora, Guido C

    2015-07-07

    Salmonella enterica serovar Typhi (S. Typhi) stg operon, encoding a chaperone/usher fimbria (CU), contributes to an increased adherence to human epithelial cells. However, one report suggests that the presence of the Stg fimbria impairs the monocyte--bacteria association, as deduced by the lower level of invasion to macrophage-like cells observed when the stg fimbrial cluster was overexpressed. Nevertheless, since other CU fimbrial structures increase the entry of S. Typhi into macrophages, and considering that transcriptomic analyses revealed that stg operon is indeed expressed in macrophages, we reassessed the role of the stg operon in the interaction between S. Typhi strain STH2370 and human cells, including macrophage-like cells and mononuclear cells directly taken from human peripheral blood. We compared S. Typhi STH2370 WT, a Chilean clinical strain, and the S. Typhi STH2370 Δstg mutant with respect to association and invasion using epithelial and macrophage-like cells. We observed that deletion of stg operon reduced the association and invasion of S. Typhi, in both cellular types. The presence of the cloned stg operon restored the WT phenotype in all the cases. Moreover, we compared Salmonella enterica sv. Typhimurium 14028s (S. Typhimurium, a serovar lacking stg operon) and S. Typhimurium heterologously expressing S. Typhi stg. We found that the latter presents an increased cell disruption of polarized epithelial cells and an increased association in both epithelial and macrophage-like cells. S. Typhi stg operon encodes a functional adhesin that participates in the interaction bacteria-eukaryotic cells, including epithelial cells and macrophages-like cells. The phenotypes associated to stg operon include increased association and consequent invasion in bacteria-eukaryotic cells, and cell disruption.

  11. Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity.

    Science.gov (United States)

    Nie, Xiao-Yan; Li, Jun-Lei; Zhang, Yong; Xu, Yang; Yang, Xue-Li; Fu, Yu; Liang, Guang-Kai; Lu, Yun; Liu, Jian; Shi, Lu-Wen

    To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG). One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs ( * 2, * 3, * 17) were genotyped and possible haplotypes were analyzed. The high on-treatment platelet reactivity (HTPR) prevalence defined by a platelet inhibition rate <30% by TEG in adenosine diphosphate (ADP)-channel was 69 (38.33%). Six common haplotypes were inferred from four of the selected P2RY12 SNPs (denoted H 0 to H 5 ) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H 1 showed a significantly lower incidence of HTPR than the reference haplotype (H 0 ) in the total study population while haplotypes H 1 and H 2 showed significantly lower incidences of HTPR than H 0 in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR. The combination of common P2RY12 variations including regulatory regions rather than rs2046934 (T744C) that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

  12. Nuclear bodies reorganize during myogenesis in vitro and are differentially disrupted by expression of FSHD-associated DUX4

    Directory of Open Access Journals (Sweden)

    Sachiko Homma

    2016-12-01

    Full Text Available Abstract Background Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handling proteins, notably TDP-43 and FUS, which have been linked to ALS pathology. Previous work showed that mouse cell line myotubes have fewer but larger nucleoli than myoblasts, and we had found that nuclear aggregation of TDP-43 in human myotubes was induced by expression of DUX4-FL, a transcription factor that is aberrantly expressed and causes pathology in facioscapulohumeral dystrophy (FSHD. However, questions remained about nuclear bodies in human myogenesis and in muscle disease. Methods We examined nucleoli, PML bodies, SC35 speckles, TDP-43, and FUS in myoblasts and myotubes derived from healthy donors and from patients with FSHD, laminin-alpha-2-deficiency (MDC1A, and alpha-sarcoglycan-deficiency (LGMD2D. We further examined how these nuclear bodies and proteins were affected by DUX4-FL expression. Results We found that nucleoli, PML bodies, and SC35 speckles reorganized during differentiation in vitro, with all three becoming less abundant in myotube vs. myoblast nuclei. In addition, though PML bodies did not change in size, both nucleoli and SC35 speckles were larger in myotube than myoblast nuclei. Similar patterns of nuclear body reorganization occurred in healthy control, MDC1A, and LGMD2D cultures, as well as in the large fraction of nuclei that did not show DUX4-FL expression in FSHD cultures. In contrast, nuclei that expressed endogenous or exogenous DUX4-FL, though retaining normal nucleoli, showed disrupted morphology of some PML bodies and most SC35 speckles and also co-aggregation of FUS with TDP-43. Conclusions Nucleoli, PML bodies, and SC35 speckles reorganize during human myotube formation in vitro. These nuclear body reorganizations are likely needed to carry out the distinct gene transcription and

  13. Endocrine Disrupting Chemicals (EDCs)

    Science.gov (United States)

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

  14. Effluent Free Radicals are Associated with Residual Renal Function and Predict Technique Failure in Peritoneal Dialysis Patients

    Science.gov (United States)

    Morinaga, Hiroshi; Sugiyama, Hitoshi; Inoue, Tatsuyuki; Takiue, Keiichi; Kikumoto, Yoko; Kitagawa, Masashi; Akagi, Shigeru; Nakao, Kazushi; Maeshima, Yohei; Miyazaki, Ikuko; Asanuma, Masato; Hiramatsu, Makoto; Makino, Hirofumi

    2012-01-01

    ♦ Objective: Residual renal function (RRF) is associated with low oxidative stress in peritoneal dialysis (PD). In the present study, we investigated the relationship between the impact of oxidative stress on RRF and patient outcomes during PD. ♦ Methods: Levels of free radicals (FRs) in effluent from the overnight dwell in 45 outpatients were determined by electron spin resonance spectrometry. The FR levels, clinical parameters, and the level of 8-hydroxy-2′-deoxyguanosine were evaluated at study start. The effects of effluent FR level on technique and patient survival were analyzed in a prospective cohort followed for 24 months. ♦ Results: Levels of effluent FRs showed significant negative correlations with daily urine volume and residual renal Kt/V, and positive correlations with plasma β2-microglobulin and effluent 8-hydroxy-2′-deoxyguanosine. A highly significant difference in technique survival (p < 0.05), but not patient survival, was observed for patients grouped by effluent FR quartile. The effluent FR level was independently associated with technique failure after adjusting for patient age, history of cardiovascular disease, and presence of diabetes mellitus (p < 0.001). The level of effluent FRs was associated with death-censored technique failure in both univariate (p < 0.001) and multivariate (p < 0.01) hazard models. Compared with patients remaining on PD, those withdrawn from the modality had significantly higher levels of effluent FRs (p < 0.005). ♦ Conclusions: Elevated effluent FRs are associated with RRF and technique failure in stable PD patients. These findings highlight the importance of oxidative stress as an unfavorable prognostic factor in PD and emphasize that steps should be taken to minimize oxidative stress in these patients. PMID:22215657

  15. Chemical and microbiological hazards associated with recycling of anaerobic digested residue intended for agricultural use

    International Nuclear Information System (INIS)

    Govasmark, Espen; Staeb, Jessica; Holen, Borge; Hoornstra, Douwe; Nesbakk, Tommy; Salkinoja-Salonen, Mirja

    2011-01-01

    In the present study, three full-scale biogas plants (BGP) were investigated for the concentration of heavy metals, organic pollutants, pesticides and the pathogenic bacteria Bacillus cereus and Escherichia coli in the anaerobically digested residues (ADR). The BGPs mainly utilize source-separated organic wastes and industrial food waste as energy sources and separate the ADR into an ADR-liquid and an ADR-solid fraction by centrifugation at the BGP. According to the Norwegian standard for organic fertilizers, the ADR were classified as quality 1 mainly because of high zinc (132-422 mg kg -1 DM) and copper (23-93 mg kg -1 DM) concentrations, but also because of high cadmium (0.21-0.60 mg kg -1 DM) concentrations in the liquid-ADR. In the screening of organic pollutants, only DEHP (9.7-62.1 mg kg -1 ) and Σ PAH 16 (0.2-1.98 mg kg -1 DM) were detected in high concentrations according to international regulations. Of the 250 pesticides analyzed, 11 were detected, but only imazalil ( -1 DM) and thiabendazol ( -1 DM) were frequently detected in the ADR-fiber. Concentrations of imazalil and thiabendazol were highest during the winter months, due to a high consumption of citrus fruits in Norway in this period. Ten percent of the ADR-liquid samples contained cereulide-producing B. cereus, whereas no verotoxigenic E. coli was detected. The authors conclude that the risk of chemical and bacterial contamination of the food chain or the environment from agricultural use of ADR seems low.

  16. Associations of adult separation anxiety disorder with conflict-related trauma, ongoing adversity, and the psychosocial disruptions of mass conflict among West Papuan refugees.

    Science.gov (United States)

    Tay, Alvin Kuowei; Rees, Susan; Kareth, Moses; Silove, Derrick

    2016-03-01

    Refugees commonly experience traumatic events that threaten the self and close others, suggesting the possibility that they may experience overlapping symptoms of posttraumatic stress disorder (PTSD) and separation anxiety disorder (SAD). We examine this possibility among West Papua refugees (n = 230) displaced to Port Moresby, Papua New Guinea. We also examine associations between the combined PTSD-SAD construct and indices of past trauma exposure, ongoing adversity, and the psychosocial disruptions caused by mass conflict and displacement. We applied culturally adapted interview modules to assess symptoms of PTSD, SAD, traumatic events (TEs), ongoing adversity, and 5 psychosocial dimensions. Latent class analysis identified a PTSD class (23%), a posttraumatic (PT) SAD class (22%), and a low-symptom class (55%). Compared with the low-symptom class, both the PTSD and PT-SAD classes endorsed higher levels of exposure to all domains of TEs (conflict-related trauma, witnessing murder, childhood related adversities, traumatic losses, and health stress) and ongoing adversity (access to health care, displacement/separation, safety in the community, and access to basic needs), but the 2 comorbid groups did not differ on these indices. The PT-SAD class alone scored higher than the low-symptom reference class in relation to disruptions to the psychosocial domains (safety/security, bonds/network, access to justice, roles/identities, existential meaning) and higher than the PTSD class on safety/security, justice and roles/identities. Our findings suggest that the PT-SAD pattern may represent a response to the most severe forms of psychosocial disruptions of mass conflict among refugees. A focus on separation anxiety may enhance psychotherapies designed to treat PTSD in refugees. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  17. In-situ observation of ULF wave activities associated with substorm expansion phase onset and current disruption

    Directory of Open Access Journals (Sweden)

    J. Liang

    2009-05-01

    Full Text Available In this paper we present two substorm events with coordinated ground-based and in-situ THEMIS observations, and focus our interest on the wave activities in Pi1 and Pi2 bands from minutes before the substorm expansion phase (EP onset to minutes after the local current disruption (CD. We find that Pi2 band (40–100 s wave appears 1–2 min before the substorm onset and last over the entire EP interval, while higher-frequency wave within Pi1 band (10–30 s emerges within few tens of seconds after the EP onset, intensifies during the local CD, and fades afterwards. The pre-onset Pi2 waves are attributed to a ballooning mode which acts as the seed perturbation to the substorm EP onset process. The azimuthal wavenumber estimated from the Doppler shift nature of the ballooning mode is consistent with the longitudinal "wavelength" inferred from the onset auroral structures. The Pi1 waves appearing within few tens of seconds after the EP onset are interpreted as supportive of a two-fluid instability mode of thin current sheet investigated in an accompanying paper (Liu and Liang, 2009. During the local CD, broadband wave activities from Pi2 band to well above the ion gyrofrequency are observed, suggesting the coexistence of various plasma instabilities featuring different frequency ranges.

  18. The formation of fire residues associated with hunter-gatherers in humid tropical environments: A geo-ethnoarchaeological perspective

    Science.gov (United States)

    Friesem, David E.; Lavi, Noa; Madella, Marco; Boaretto, Elisabetta; Ajithparsad, P.; French, Charles

    2017-09-01

    Tropical forests have been an important human habitat and played a significant role in early human dispersal and evolution. Likewise, the use of fire, besides being one of the exceptional characteristics of humans, serves as a marker for human evolution. While the use of fire by prehistoric hunter-gatherers is relatively well documented in arid and temperate environments, the archaeological evidence in humid tropical environment is to date very limited. We first review the archaeological evidence for hunter-gatherer use of fire in humid tropical environments and suggest that better understanding of formation processes is required. We present a geo-ethnoarchaeological study from South India, involving ethnography, excavations and laboratory-based analyses in order to build a new framework to study fire residues in humid tropical forests associated with hunter-gatherer's use of fire. Ethnographic observations point to a dynamic and ephemeral use of hearths. Hearths location were dictated by the social and ever-changing social dynamics of the site. The hearths deposited small amount of residues which were later swept on a daily basis, re-depositing ash and charcoal in waste areas and leaving only a microscopic signal in the original location. Particular acidic conditions and intensive biological activity within tropical sediments result in the complete dissolution of ash and bones while favouring the preservation of charcoal and phytoliths. Consequently, the identification of fire residues in humid tropical forests and the reconstruction of the human use of fire must involve multi-proxy microscopic analysis to detect its micro-signatures.

  19. Patterns of family instability and crime: The association of timing of the family's disruption with subsequent adolescent and young adult criminality.

    Science.gov (United States)

    Mednick, B R; Baker, R L; Carothers, L E

    1990-06-01

    This study provides a longitudinal view of selected correlates of family disruption and suggests how they may contribute to adolescent and young adult criminal behavior. Data from a sample of 410 males, ages 19-21, who took part in an 18-year follow-up study of a Danish Prospective Perinatal Cohort, were used. Paternal crime, descriptions of the families'patterns of stability, and socioeconomic status changes over the life of the offspring were examined to determine their association with official records of adolescent and young adult crime. Analyses showed that divorce followed by a stable family constellation was notassociated with increased risk of criminal behavior, whereas divorce followed by additional changes in family constellations significantly increased the risk. Age at onset of child criminality was notrelated to stability patterns. Males experiencing continued instability during adolescence were especially at risk. Downward changes in SES and record of paternal crime both showed independent associations with offspring crime.

  20. Neonicotinoid insecticide residues in surface water and soil associated with commercial maize (corn) fields in southwestern Ontario.

    Science.gov (United States)

    Schaafsma, Arthur; Limay-Rios, Victor; Baute, Tracey; Smith, Jocelyn; Xue, Yingen

    2015-01-01

    Neonicotinoid insecticides have come under scrutiny for their potential unintended effects on non-target organisms, particularly pollinators in agro-ecosystems. As part of a larger study of neonicotinoid residues associated with maize (corn) production, 76 water samples within or around the perimeter of 18 commercial maize fields and neighbouring apiaries were collected in 5 maize-producing counties of southwestern Ontario. Residues of clothianidin (mean = 2.28, max. = 43.60 ng/mL) and thiamethoxam (mean = 1.12, max. = 16.50 ng/mL) were detected in 100 and 98.7% of the water samples tested, respectively. The concentration of total neonicotinoid residues in water within maize fields increased six-fold during the first five weeks after planting, and returned to pre-plant levels seven weeks after planting. However, concentrations in water sampled from outside the fields were similar throughout the sampling period. Soil samples from the top 5 cm of the soil profile were also collected in these fields before and immediately following planting. The mean total neonicotinoid residue was 4.02 (range 0.07 to 20.30) ng/g, for samples taken before planting, and 9.94 (range 0.53 to 38.98) ng/g, for those taken immediately after planting. Two soil samples collected from within an conservation area contained detectable (0.03 and 0.11 ng/g) concentrations of clothianidin. Of three drifted snow samples taken, the drift stratum containing the most wind-scoured soil had 0.16 and 0.20 ng/mL mainly clothianidin in the melted snow. The concentration was at the limit of detection (0.02 ng/mL) taken across the entire vertical profile. With the exception of one sample, water samples tested had concentrations below those reported to have acute, chronic or sublethal effects to honey bees. Our results suggest that neonicotinoids may move off-target by wind erosion of contaminated soil. These results are informative to risk assessment models for other non-target species in maize agro-ecosytems.

  1. Neonicotinoid insecticide residues in surface water and soil associated with commercial maize (corn fields in southwestern Ontario.

    Directory of Open Access Journals (Sweden)

    Arthur Schaafsma

    Full Text Available Neonicotinoid insecticides have come under scrutiny for their potential unintended effects on non-target organisms, particularly pollinators in agro-ecosystems. As part of a larger study of neonicotinoid residues associated with maize (corn production, 76 water samples within or around the perimeter of 18 commercial maize fields and neighbouring apiaries were collected in 5 maize-producing counties of southwestern Ontario. Residues of clothianidin (mean = 2.28, max. = 43.60 ng/mL and thiamethoxam (mean = 1.12, max. = 16.50 ng/mL were detected in 100 and 98.7% of the water samples tested, respectively. The concentration of total neonicotinoid residues in water within maize fields increased six-fold during the first five weeks after planting, and returned to pre-plant levels seven weeks after planting. However, concentrations in water sampled from outside the fields were similar throughout the sampling period. Soil samples from the top 5 cm of the soil profile were also collected in these fields before and immediately following planting. The mean total neonicotinoid residue was 4.02 (range 0.07 to 20.30 ng/g, for samples taken before planting, and 9.94 (range 0.53 to 38.98 ng/g, for those taken immediately after planting. Two soil samples collected from within an conservation area contained detectable (0.03 and 0.11 ng/g concentrations of clothianidin. Of three drifted snow samples taken, the drift stratum containing the most wind-scoured soil had 0.16 and 0.20 ng/mL mainly clothianidin in the melted snow. The concentration was at the limit of detection (0.02 ng/mL taken across the entire vertical profile. With the exception of one sample, water samples tested had concentrations below those reported to have acute, chronic or sublethal effects to honey bees. Our results suggest that neonicotinoids may move off-target by wind erosion of contaminated soil. These results are informative to risk assessment models for other non-target species in maize

  2. Neonicotinoid Insecticide Residues in Surface Water and Soil Associated with Commercial Maize (Corn) Fields in Southwestern Ontario

    Science.gov (United States)

    Schaafsma, Arthur; Limay-Rios, Victor; Baute, Tracey; Smith, Jocelyn; Xue, Yingen

    2015-01-01

    Neonicotinoid insecticides have come under scrutiny for their potential unintended effects on non-target organisms, particularly pollinators in agro-ecosystems. As part of a larger study of neonicotinoid residues associated with maize (corn) production, 76 water samples within or around the perimeter of 18 commercial maize fields and neighbouring apiaries were collected in 5 maize-producing counties of southwestern Ontario. Residues of clothianidin (mean = 2.28, max. = 43.60 ng/mL) and thiamethoxam (mean = 1.12, max. = 16.50 ng/mL) were detected in 100 and 98.7% of the water samples tested, respectively. The concentration of total neonicotinoid residues in water within maize fields increased six-fold during the first five weeks after planting, and returned to pre-plant levels seven weeks after planting. However, concentrations in water sampled from outside the fields were similar throughout the sampling period. Soil samples from the top 5 cm of the soil profile were also collected in these fields before and immediately following planting. The mean total neonicotinoid residue was 4.02 (range 0.07 to 20.30) ng/g, for samples taken before planting, and 9.94 (range 0.53 to 38.98) ng/g, for those taken immediately after planting. Two soil samples collected from within an conservation area contained detectable (0.03 and 0.11 ng/g) concentrations of clothianidin. Of three drifted snow samples taken, the drift stratum containing the most wind-scoured soil had 0.16 and 0.20 ng/mL mainly clothianidin in the melted snow. The concentration was at the limit of detection (0.02 ng/mL) taken across the entire vertical profile. With the exception of one sample, water samples tested had concentrations below those reported to have acute, chronic or sublethal effects to honey bees. Our results suggest that neonicotinoids may move off-target by wind erosion of contaminated soil. These results are informative to risk assessment models for other non-target species in maize agro

  3. Disruptive Mood Dysregulation Disorder Symptoms and Association with Oppositional Defiant and Other Disorders in a General Population Child Sample.

    Science.gov (United States)

    Mayes, Susan D; Waxmonsky, James D; Calhoun, Susan L; Bixler, Edward O

    2016-03-01

    The new Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) diagnosis, disruptive mood dysregulation disorder (DMDD), has generated appreciable controversy since its inception, primarily in regard to its validity as a distinct disorder from oppositional defiant disorder (ODD). The goal of our study was to determine if the two DSM-5 DMDD symptoms (persistently irritable or angry mood and severe recurrent temper outbursts) occurred independently of other disorders, particularly ODD. Other DSM-5 DMDD criteria were not assessed. Maternal ratings of the two DMDD symptoms, clinical diagnosis of ODD using DSM-5 symptom criteria, and psychological problem scores (anxiety, depression, oppositional behavior, conduct disorder, and attention-deficit/hyperactivity disorder [ADHD]) on the Pediatric Behavior Scale were analyzed in a population sample, 6-12 years of age (n = 665). The prevalence of DMDD symptoms (irritable-angry mood and temper outbursts both rated by mothers as often or very often a problem) was 9%. In all, 92% of children with DMDD symptoms had ODD, and 66% of children with ODD had DMDD symptoms, indicating that it is very unlikely to have DMDD symptoms without ODD, but that ODD can occur without DMDD symptoms. Comorbid psychological problems (anxiety, depression, conduct disorder, and ADHD) in addition to ODD did not increase the risk of having DMDD symptoms beyond that for ODD alone. Only 3% of children with psychological problems other than ODD had DMDD symptoms. Our general population findings are similar to those for a psychiatric sample, suggesting that DMDD cannot be differentiated from ODD based on symptomatology. Therefore, it is important to assess all DSM criteria and to examine for comorbid psychopathology when considering a diagnosis of DMDD. Our results support the recommendation made by the World Health Organization's International Classification of Diseases, 11th Revision (ICD-11) panel of experts that DMDD symptoms may be

  4. Ecological risk assessment associated to the removal of endocrine-disrupting parabens and benzophenone-4 in wastewater treatment.

    Science.gov (United States)

    Molins-Delgado, Daniel; Díaz-Cruz, M Silvia; Barceló, Damià

    2016-06-05

    The occurrence of four widely used and endocrine disrupting parabens (PBs) (methylparaben, propylparaben, butylparaben and benzylparaben) and a polar UV filter (benzophenone-4) were determined in influent and effluent wastewater from the 19 major wastewater treatment plants (WWTPs) of Catalonia, Spain. For their analysis an on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method was developed and validated. Laboratory analysis revealed high levels for both PBs and BP4, with maximum concentrations of 5700ngL(-1) and 1806ngL(-1), respectively, in influent samples, and 137ngL(-1) and 1080ngL(-1), respectively in effluent wastewaters. Removal rates (RE%) for the target compounds in each WWTPs were calculated. RE% for parabens were almost 100%, whereas for BP4 values where in the range 5-91%. The half-life time (t1/2), hydraulic retention time (HRT), and annual mass load (ML) for each facility was estimated. Results indicated that there was no clear influence of HRT on the RE% of BP4. MLs for BP4 were in the range 0.9-110.1kgy(-1), with the highest values in the most populated areas. Finally, a risk assessment, estimated in terms of hazard quotients (HQs), was carried out for aquatic biota. HQs for the target compounds in effluent wastewaters indicated a negligible effect, whereas for some influent wastewaters' HQs pointed out that some species are at risk. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Amino acid residue 67 (isoleucine) of HLA-DRB is associated with POHS

    NARCIS (Netherlands)

    Ongkosuwito, Jenny V.; Tilanus, Marcel G. J.; van der Lelij, Allegonda; van Schooneveld, Mary J.; Jager, Martine J.; Rozemuller, Erik H.; de Smet, Marc D.; Suttorp-Schulten, Maria S. A.

    2002-01-01

    PURPOSE. To investigate whether presumed ocular histoplasmosis syndrome (POHS) in The Netherlands is associated with HLA-DR2 and HLA-B7, as previously shown in the United States. METHODS. Twenty-four Dutch patients with POHS were included in this study. DNA isolated from peripheral blood leukocytes

  6. A residue-specific view of the association and dissociation pathway in protein−DNA recognition

    NARCIS (Netherlands)

    Kalodimos, Ch.; Boelens, R.|info:eu-repo/dai/nl/070151407; Kaptein, R.|info:eu-repo/dai/nl/074334603

    2002-01-01

    Signal propagation in biological systems occurs through a series of inter- and intramolecular events, the precise pathways of which remain elusive in most cases. With respect to protein−DNA interactions in particular, little is known about the association and dissociation reaction pathways. Here we

  7. Variation in one residue associated with the metal ion-dependent adhesion site regulates αIIbβ3 integrin ligand binding affinity.

    Directory of Open Access Journals (Sweden)

    Joel Raborn

    Full Text Available The Asp of the RGD motif of the ligand coordinates with the β I domain metal ion dependent adhesion site (MIDAS divalent cation, emphasizing the importance of the MIDAS in ligand binding. There appears to be two distinct groups of integrins that differ in their ligand binding affinity and adhesion ability. These differences may be due to a specific residue associated with the MIDAS, particularly the β3 residue Ala(252 and corresponding Ala in the β1 integrin compared to the analogous Asp residue in the β2 and β7 integrins. Interestingly, mutations in the adjacent to MIDAS (ADMIDAS of integrins α4β7 and αLβ2 increased the binding and adhesion abilities compared to the wild-type, while the same mutations in the α2β1, α5β1, αVβ3, and αIIbβ3 integrins demonstrated decreased ligand binding and adhesion. We introduced a mutation in the αIIbβ3 to convert this MIDAS associated Ala(252 to Asp. By combination of this mutant with mutations of one or two ADMIDAS residues, we studied the effects of this residue on ligand binding and adhesion. Then, we performed molecular dynamics simulations on the wild-type and mutant αIIbβ3 integrin β I domains, and investigated the dynamics of metal ion binding sites in different integrin-RGD complexes. We found that the tendency of calculated binding free energies was in excellent agreement with the experimental results, suggesting that the variation in this MIDAS associated residue accounts for the differences in ligand binding and adhesion among different integrins, and it accounts for the conflicting results of ADMIDAS mutations within different integrins. This study sheds more light on the role of the MIDAS associated residue pertaining to ligand binding and adhesion and suggests that this residue may play a pivotal role in integrin-mediated cell rolling and firm adhesion.

  8. RISKS ASSOCIATED WITH THE PRESENCE OF ANTIMICROBIAL DRUG RESIDUES IN MEAT PRODUCTS AND PRODUCTS OF ANIMAL SLAUGHTER

    Directory of Open Access Journals (Sweden)

    D. S. Bataeva

    2016-01-01

    Full Text Available The risks associated with the presence of antimicrobial drug residues in meat and products of animal slaughter were determined. One of them is the emergence of antimicrobial resistance in pathogenic and conditionally pathogenic microorganisms isolated from meat and products of animal slaughter. It was established that Escherichia coli, Salmonella and Pseudomonas were resistant to ampicillin, tetracycline, tylosin and cephalolexin. However, Listeria monocytogenes did not have resistance to these antibiotics. It was also established that when entering an animal body, antimicrobials were accumulated mostly in liver and kidneys of an animal followed by meat and, to the least degree, in fat. It was found that up to 65% of the tested samples were contaminated with antimicrobials to a greater or lesser degree.

  9. Contaminant Release from Residual Waste in Closed Single-Shell Tanks and Other Waste Forms Associated with the Tanks

    International Nuclear Information System (INIS)

    Deutsch, William J.

    2008-01-01

    This chapter describes the release of contaminants from the various waste forms that are anticipated to be associated with closure of the single-shell tanks. These waste forms include residual sludge or saltcake that will remain in the tanks after waste retrieval. Other waste forms include engineered glass and cementitious materials as well as contaminated soil impacted by previous tank leaks. This chapter also describes laboratory testing to quantify contaminant release and how the release data are used in performance/risk assessments for the tank waste management units and the onsite waste disposal facilities. The chapter ends with a discussion of the surprises and lessons learned to date from the testing of waste materials and the development of contaminant release models

  10. Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology.

    Science.gov (United States)

    Chiu, Yu-Han; Williams, Paige L; Gillman, Matthew W; Gaskins, Audrey J; Mínguez-Alarcón, Lidia; Souter, Irene; Toth, Thomas L; Ford, Jennifer B; Hauser, Russ; Chavarro, Jorge E

    2018-01-01

    Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART). This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high- and low-pesticide residue FV intake with ART outcomes. Adjusted probabilities of clinical pregnancy and live birth per treatment cycle. In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high- and low-pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high-pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (women in the highest quartile (≥2.3 servings/d) had 18% (95% CI, 5%-30%) lower probability of clinical pregnancy and 26% (95% CI, 13%-37%) lower probability of live birth. Intake of low-pesticide residue FVs was not significantly related to ART outcomes. Higher consumption of high-pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences.

  11. Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag.

    Science.gov (United States)

    Friedrich, Melanie; Setz, Christian; Hahn, Friedrich; Matthaei, Alina; Fraedrich, Kirsten; Rauch, Pia; Henklein, Petra; Traxdorf, Maximilian; Fossen, Torgils; Schubert, Ulrich

    2016-04-25

    The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (L-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

  12. Disruption of rolandic gamma-band functional connectivity by seizures is associated with motor impairments in children with epilepsy.

    Directory of Open Access Journals (Sweden)

    George M Ibrahim

    Full Text Available Although children with epilepsy exhibit numerous neurological and cognitive deficits, the mechanisms underlying these impairments remain unclear. Synchronization of oscillatory neural activity in the gamma frequency range (>30 Hz is purported to be a mechanism mediating functional integration within neuronal networks supporting cognition, perception and action. Here, we tested the hypothesis that seizure-induced alterations in gamma synchronization are associated with functional deficits. By calculating synchrony among electrodes and performing graph theoretical analysis, we assessed functional connectivity and local network structure of the hand motor area of children with focal epilepsy from intracranial electroencephalographic recordings. A local decrease in inter-electrode phase synchrony in the gamma bands during ictal periods, relative to interictal periods, within the motor cortex was strongly associated with clinical motor weakness. Gamma-band ictal desychronization was a stronger predictor of deficits than the presence of the seizure-onset zone or lesion within the motor cortex. There was a positive correlation between the magnitude of ictal desychronization and impairment of motor dexterity in the contralateral, but not ipsilateral hand. There was no association between ictal desynchronization within the hand motor area and non-motor deficits. This study uniquely demonstrates that seizure-induced disturbances in cortical functional connectivity are associated with network-specific neurological deficits.

  13. Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Tibu, F; Sheridan, M A; McLaughlin, K A; Nelson, C A; Fox, N A; Zeanah, C H

    2016-02-01

    Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. A sample of 136 children (aged 6-30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners' offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.

  14. Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity.

    Science.gov (United States)

    Ombrello, Michael J; Kirino, Yohei; de Bakker, Paul I W; Gül, Ahmet; Kastner, Daniel L; Remmers, Elaine F

    2014-06-17

    The HLA protein, HLA-B*51, encoded by HLA-B in MHC, is the strongest known genetic risk factor for Behçet disease (BD). Associations between BD and other factors within the MHC have been reported also, although strong regional linkage disequilibrium complicates their confident disentanglement from HLA-B*51. In the current study, we examined a combination of directly obtained and imputed MHC-region SNPs, directly obtained HLA-B locus types, and imputed classical HLA types with their corresponding polymorphic amino acid residues for association with BD in 1,190 cases and 1,257 controls. SNP mapping with logistic regression of the MHC identified the HLA-B/MICA region and the region between HLA-F and HLA-A as independently associated with BD (P MHC class I (MHC-I) amino acid residues, including anchor residues that critically define the selection and binding of peptides to MHC-I molecules, residues known to influence MHC-I-killer immunoglobulin-like receptor interactions, and a residue located in the signal peptide of HLA-B. The locations of these variants collectively implicate MHC-I peptide binding in the pathophysiology of BD. Furthermore, several lines of evidence suggest a role for altered regulation of cellular cytotoxicity in BD pathogenesis.

  15. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC

    DEFF Research Database (Denmark)

    Garbarino, J.; Pan, M. H.; Chin, H. F.

    2012-01-01

    STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the non-vesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using...... small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT...... synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein...

  16. Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip

    DEFF Research Database (Denmark)

    Rahimov, Fedik; Marazita, Mary L; Visel, Axel

    2008-01-01

    Previously we have shown that nonsyndromic cleft lip with or without cleft palate (NSCL/P) is strongly associated with SNPs in IRF6 (interferon regulatory factor 6). Here, we use multispecies sequence comparisons to identify a common SNP (rs642961, G>A) in a newly identified IRF6 enhancer....... The A allele is significantly overtransmitted (P = 1 x 10(-11)) in families with NSCL/P, in particular those with cleft lip but not cleft palate. Further, there is a dosage effect of the A allele, with a relative risk for cleft lip of 1.68 for the AG genotype and 2.40 for the AA genotype. EMSA and ChIP assays...

  17. Longitudinal associations between maternal disrupted representations, maternal interactive behavior and infant attachment: A comparison between full-term and preterm dyads

    NARCIS (Netherlands)

    Hall, R.A.S.; Hoffenkamp, H.N.; Tooten, A.; Braeken, J.; Vingerhoets, A.J.J.M.; van Bakel, H.J.A.

    2015-01-01

    This prospective study examined whether or not a mother’s representations of her infant were more often disrupted after premature childbirth. Furthermore, the study examined if different components of maternal interactive behavior mediated the relation between maternal disrupted representations and

  18. Properties of soil pore space regulate pathways of plant residue decomposition and community structure of associated bacteria.

    Science.gov (United States)

    Negassa, Wakene C; Guber, Andrey K; Kravchenko, Alexandra N; Marsh, Terence L; Hildebrandt, Britton; Rivers, Mark L

    2015-01-01

    Physical protection of soil carbon (C) is one of the important components of C storage. However, its exact mechanisms are still not sufficiently lucid. The goal of this study was to explore the influence of soil structure, that is, soil pore spatial arrangements, with and without presence of plant residue on (i) decomposition of added plant residue, (ii) CO2 emission from soil, and (iii) structure of soil bacterial communities. The study consisted of several soil incubation experiments with samples of contrasting pore characteristics with/without plant residue, accompanied by X-ray micro-tomographic analyses of soil pores and by microbial community analysis of amplified 16S-18S rRNA genes via pyrosequencing. We observed that in the samples with substantial presence of air-filled well-connected large (>30 µm) pores, 75-80% of the added plant residue was decomposed, cumulative CO2 emission constituted 1,200 µm C g(-1) soil, and movement of C from decomposing plant residue into adjacent soil was insignificant. In the samples with greater abundance of water-filled small pores, 60% of the added plant residue was decomposed, cumulative CO2 emission constituted 2,000 µm C g(-1) soil, and the movement of residue C into adjacent soil was substantial. In the absence of plant residue the influence of pore characteristics on CO2 emission, that is on decomposition of the native soil organic C, was negligible. The microbial communities on the plant residue in the samples with large pores had more microbial groups known to be cellulose decomposers, that is, Bacteroidetes, Proteobacteria, Actinobacteria, and Firmicutes, while a number of oligotrophic Acidobacteria groups were more abundant on the plant residue from the samples with small pores. This study provides the first experimental evidence that characteristics of soil pores and their air/water flow status determine the phylogenetic composition of the local microbial community and directions and magnitudes of soil C

  19. Properties of soil pore space regulate pathways of plant residue decomposition and community structure of associated bacteria.

    Directory of Open Access Journals (Sweden)

    Wakene C Negassa

    Full Text Available Physical protection of soil carbon (C is one of the important components of C storage. However, its exact mechanisms are still not sufficiently lucid. The goal of this study was to explore the influence of soil structure, that is, soil pore spatial arrangements, with and without presence of plant residue on (i decomposition of added plant residue, (ii CO2 emission from soil, and (iii structure of soil bacterial communities. The study consisted of several soil incubation experiments with samples of contrasting pore characteristics with/without plant residue, accompanied by X-ray micro-tomographic analyses of soil pores and by microbial community analysis of amplified 16S-18S rRNA genes via pyrosequencing. We observed that in the samples with substantial presence of air-filled well-connected large (>30 µm pores, 75-80% of the added plant residue was decomposed, cumulative CO2 emission constituted 1,200 µm C g(-1 soil, and movement of C from decomposing plant residue into adjacent soil was insignificant. In the samples with greater abundance of water-filled small pores, 60% of the added plant residue was decomposed, cumulative CO2 emission constituted 2,000 µm C g(-1 soil, and the movement of residue C into adjacent soil was substantial. In the absence of plant residue the influence of pore characteristics on CO2 emission, that is on decomposition of the native soil organic C, was negligible. The microbial communities on the plant residue in the samples with large pores had more microbial groups known to be cellulose decomposers, that is, Bacteroidetes, Proteobacteria, Actinobacteria, and Firmicutes, while a number of oligotrophic Acidobacteria groups were more abundant on the plant residue from the samples with small pores. This study provides the first experimental evidence that characteristics of soil pores and their air/water flow status determine the phylogenetic composition of the local microbial community and directions and magnitudes of

  20. Properties of Soil Pore Space Regulate Pathways of Plant Residue Decomposition and Community Structure of Associated Bacteria

    Science.gov (United States)

    Negassa, Wakene C.; Guber, Andrey K.; Kravchenko, Alexandra N.; Marsh, Terence L.; Hildebrandt, Britton; Rivers, Mark L.

    2015-01-01

    Physical protection of soil carbon (C) is one of the important components of C storage. However, its exact mechanisms are still not sufficiently lucid. The goal of this study was to explore the influence of soil structure, that is, soil pore spatial arrangements, with and without presence of plant residue on (i) decomposition of added plant residue, (ii) CO2 emission from soil, and (iii) structure of soil bacterial communities. The study consisted of several soil incubation experiments with samples of contrasting pore characteristics with/without plant residue, accompanied by X-ray micro-tomographic analyses of soil pores and by microbial community analysis of amplified 16S–18S rRNA genes via pyrosequencing. We observed that in the samples with substantial presence of air-filled well-connected large (>30 µm) pores, 75–80% of the added plant residue was decomposed, cumulative CO2 emission constituted 1,200 µm C g-1 soil, and movement of C from decomposing plant residue into adjacent soil was insignificant. In the samples with greater abundance of water-filled small pores, 60% of the added plant residue was decomposed, cumulative CO2 emission constituted 2,000 µm C g-1 soil, and the movement of residue C into adjacent soil was substantial. In the absence of plant residue the influence of pore characteristics on CO2 emission, that is on decomposition of the native soil organic C, was negligible. The microbial communities on the plant residue in the samples with large pores had more microbial groups known to be cellulose decomposers, that is, Bacteroidetes, Proteobacteria, Actinobacteria, and Firmicutes, while a number of oligotrophic Acidobacteria groups were more abundant on the plant residue from the samples with small pores. This study provides the first experimental evidence that characteristics of soil pores and their air/water flow status determine the phylogenetic composition of the local microbial community and directions and magnitudes of soil C

  1. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC.

    Science.gov (United States)

    Garbarino, Jeanne; Pan, Meihui; Chin, Harvey F; Lund, Frederik W; Maxfield, Frederick R; Breslow, Jan L

    2012-12-01

    STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the nonvesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein receptor (LDLR) levels were increased and decreased, respectively. We also observed a decrease in NPC1 protein expression, suggesting the induction of compensatory pathways to maintain cholesterol balance. These data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well.

  2. Acute exposure to selenium disrupts associative conditioning and long-term memory recall in honey bees (Apis mellifera).

    Science.gov (United States)

    Burden, Christina M; Elmore, Christopher; Hladun, Kristen R; Trumble, John T; Smith, Brian H

    2016-05-01

    A plethora of toxic compounds - including pesticides, heavy metals, and metalloids - have been detected in honey bees (Apis mellifera) and their colonies. One such compound is selenium, which bees are exposed to by consuming nectar and pollen from flowers grown in contaminated areas. Though selenium is lethal at high concentrations, sublethal exposure may also impair honey bees' ability to function normally. Examining the effect of selenium exposure on learning and memory provides a sensitive assay with which to identify sublethal effects on honey bee health and behavior. To determine whether sublethal selenium exposure causes learning and memory deficits, we used proboscis extension reflex conditioning coupled with recall tests 30min and 24h post-conditioning. We exposed forager honey bees to a single sublethal dose of selenium, and 3h later we used an olfactory conditioning assay to train the bees to discriminate between one odor associated with sucrose-reinforcement and a second unreinforced odor. Following conditioning we tested short- and long-term recall of the task. Acute exposure to as little as 1.8ng of an inorganic form of selenium (sodium selenate) before conditioning caused a reduction in behavioral performance during conditioning. And, exposure to 18ng of either an inorganic form (sodium selenate) or an organic form (methylseleno-l-cysteine) of selenium caused a reduction in the bees' performance during the long-term recall test. These concentrations of selenium are lower than those found in the nectar of plants grown in selenium-contaminated soil, indicating that even low-grade selenium toxicity produces significant learning and memory impairments. This may reduce foragers' ability to effectively gather resources for the colony or nurse bees' ability to care for and maintain a healthy colony. Copyright © 2016. Published by Elsevier Inc.

  3. Regular treadmill exercise prevents sleep deprivation-induced disruption of synaptic plasticity and associated signaling cascade in the dentate gyrus.

    Science.gov (United States)

    Zagaar, Munder; Dao, An; Alhaider, Ibrahim; Alkadhi, Karim

    2013-09-01

    Evidence suggests that regular exercise can protect against learning and memory impairment in the presence of insults such as sleep deprivation. The dentate gyrus (DG) area of the hippocampus is a key staging area for learning and memory processes and is particularly sensitive to sleep deprivation. The purpose of this study was to determine the effect of regular exercise on early-phase long-term potentiation (E-LTP) and its signaling cascade in the presence of sleep deprivation. Rats were exposed to 4 weeks of regular treadmill exercise then subsequently sleep-deprived for 24h using the modified multiple platform model before experimentation. We tested the effects of exercise and/or sleep deprivation using electrophysiological recording in the DG to measure synaptic plasticity; and Western blot analysis to quantify the levels of key signaling proteins related to E-LTP. Regular exercise prevented the sleep deprivation-induced impairment of E-LTP in the DG area as well as the sleep deprivation-associated decrease in basal protein levels of phosphorylated and total α calcium/calmodulin-dependent protein kinase II (P/total-CaMKII) and brain-derived neurotrophic factor (BDNF). High frequency stimulation (HFS) to the DG area was used to model learning stimuli and increased the P-CaMKII and BDNF levels in normal animals: yet failed to change these levels in sleep-deprived rats. However, HFS in control and sleep-deprived rats increased the levels of the phosphatase calcineurin. In contrast, exercise increased BDNF and P-CaMKII levels in exercised/sleep-deprived rats. Regular exercise appears to exert a protective effect against sleep deprivation-induced spatial memory impairment by inducing hippocampal signaling cascades that positively modulate basal and stimulated levels of key effectors such as P-CaMKII and BDNF, while attenuating increases in the protein phosphatase calcineurin. © 2013.

  4. Study of the experimental parameters associated to the determination of residual macro stresses in stainless steel tubes through x-rays diffraction method

    International Nuclear Information System (INIS)

    Guimaraes, L.R.

    1990-01-01

    The basic principles related to the determination of residual macro stresses by X-rays diffractometry are present, whereas different techniques associated with the respective experimental errors are discussed. The residual stresses in two 304 L stainless steel tubes were measured using three models of diffractometers, Rigaku SG-8, Jeol JDX-11PA and Rigaku Strainflex. The measured values of stresses as well as the reproducibilities are examined. The suitability of peak location method, by fitting three data points to the parabolic function, is discussed through values of position and intensity obtained by two of the above diffractometers. (author)

  5. Study of the experimental parameters associated to the determination of residual macro stresses in stainless steel tubes, through x-ray diffraction method

    International Nuclear Information System (INIS)

    Guimaraes, L.R.

    1990-01-01

    The basic principles related to the determination of residual macro stresses by X-rays diffractometry are present, whereas different techniques associated with the respective experimental errors are discussed. The residual stresses in two 304 L stainless steel tubes were measured using three models of diffractometers, Rigaku SG-8, Jeol JDX-11PA and Rigaku Strainflex. The measured values of stresses as well as the reproducibilities are examined. The suitability of peak location method, by fitting three data points to the parabolic function, is discussed through values of position and intensity obtained by two of the above diffractometers. (author)

  6. Urine, peritoneal fluid and omental fat proteomes of reproductive age women: Endometriosis-related changes and associations with endocrine disrupting chemicals.

    Science.gov (United States)

    Williams, Katherine E; Miroshnychenko, Olga; Johansen, Eric B; Niles, Richard K; Sundaram, Rajeshwari; Kannan, Kurunthachalam; Albertolle, Matthew; Zhou, Yan; Prasad, Namrata; Drake, Penelope M; Giudice, Linda C; Hall, Steven C; Witkowska, H Ewa; Buck Louis, Germaine M; Fisher, Susan J

    2015-01-15

    Endometriosis, ectopic growth of the uterine lining (endometrium), which affects 6-11% of reproductive age women, is associated with pelvic pain and infertility. We investigated the peritoneal fluid (PF), urine and omental fat (OF) proteomes of women with endometriosis vs. individuals with no surgically visualized endometriosis. All participants were enrolled in the NICHD-funded ENDO Study. A two-step proteomic study was performed. The first, a broad survey, employed a semi-quantitative gel LC-mass spectrometry (MS) workflow: SDS PAGE fractionation, trypsin digestion and LC-MS/MS. The results showed sample integrity but failed to detect any differences between women with and without endometriosis. The second step was a quantitative analysis of OF samples. We employed another sample set (n=30) from women ± disease and isobaric mass-tag (iTRAQ) chemistry to label peptides and 2D LC-MS/MS for protein identification and quantification. Three proteins-matrix metalloproteinase-9, neutrophil elastase, and FAM49B-were significantly lower in abundance in samples from women with endometriosis. Interestingly, neutrophil elastase and FAM49B levels were associated with higher levels of a subset of endocrine disrupting chemicals (EDCs) that were previously measured in the same samples. The results of these experiments showed the feasibility of associating endometriosis with changes in the OF protein repertoire and EDC levels. Endometriosis, pathological growth of the uterine lining, is associated with significant morbidities, including pain and infertility. However, the causes of this common condition are poorly understood. This study determined whether endometriosis was associated with changes in the protein composition of peritoneal fluid, urine and/or omental fat. A protein of unknown function (FAM49B) and two proteinases (metalloproteinase-9, neutrophil elastase) were down regulated in OF samples from women with versus without endometriosis. These findings suggested

  7. A SNP in steroid receptor coactivator-1 disrupts a GSK3β phosphorylation site and is associated with altered tamoxifen response in bone.

    Science.gov (United States)

    Hartmaier, R J; Richter, A S; Gillihan, R M; Sallit, J Z; McGuire, S E; Wang, J; Lee, A V; Osborne, C K; O'Malley, B W; Brown, P H; Xu, J; Skaar, T C; Philips, S; Rae, J M; Azzouz, F; Li, L; Hayden, J; Henry, N L; Nguyen, A T; Stearns, V; Hayes, D F; Flockhart, D A; Oesterreich, S

    2012-02-01

    The coregulator steroid receptor coactivator (SRC)-1 increases transcriptional activity of the estrogen receptor (ER) in a number of tissues including bone. Mice deficient in SRC-1 are osteopenic and display skeletal resistance to estrogen treatment. SRC-1 is also known to modulate effects of selective ER modulators like tamoxifen. We hypothesized that single nucleotide polymorphisms (SNP) in SRC-1 may impact estrogen and/or tamoxifen action. Because the only nonsynonymous SNP in SRC-1 (rs1804645; P1272S) is located in an activation domain, it was examined for effects on estrogen and tamoxifen action. SRC-1 P1272S showed a decreased ability to coactivate ER compared with wild-type SRC-1 in multiple cell lines. Paradoxically, SRC-1 P1272S had an increased protein half-life. The Pro to Ser change disrupts a putative glycogen synthase 3 (GSK3)β phosphorylation site that was confirmed by in vitro kinase assays. Finally, knockdown of GSK3β increased SRC-1 protein levels, mimicking the loss of phosphorylation at P1272S. These findings are similar to the GSK3β-mediated phospho-ubiquitin clock previously described for the related coregulator SRC-3. To assess the potential clinical significance of this SNP, we examined whether there was an association between SRC-1 P1272S and selective ER modulators response in bone. SRC-1 P1272S was associated with a decrease in hip and lumbar bone mineral density in women receiving tamoxifen treatment, supporting our in vitro findings for decreased ER coactivation. In summary, we have identified a functional genetic variant of SRC-1 with decreased activity, resulting, at least in part, from the loss of a GSK3β phosphorylation site, which was also associated with decreased bone mineral density in tamoxifen-treated women.

  8. Understanding the relative contributions of direct environmental effects and passive genotype-environment correlations in the association between familial risk factors and child disruptive behavior disorders.

    Science.gov (United States)

    Bornovalova, M A; Cummings, J R; Hunt, E; Blazei, R; Malone, S; Iacono, W G

    2014-03-01

    Previous work reports an association between familial risk factors stemming from parental characteristics and offspring disruptive behavior disorders (DBDs). This association may reflect (a) the direct effects of familial environment and (b) a passive gene-environment correlation (r(GE)), wherein the parents provide both the genes and the environment. The current study examined the contributions of direct environmental influences and passive r(GE) by comparing the effects of familial risk factors on child DBDs in genetically related (biological) and non-related (adoptive) families. Participants were 402 adoptive and 204 biological families. Familial environment was defined as maternal and paternal maladaptive parenting and antisociality, marital conflict and divorce; offspring DBDs included attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Mixed-level regressions estimated the main effects of familial environment, adoption status and the familial environment by adoption status interaction term, which tested for the presence of passive r(GE). There was a main effect of maternal and paternal maladaptive parenting and marital discord on child DBDs, indicating a direct environmental effect. There was no direct environmental effect of maternal or paternal antisociality, but maternal and paternal antisociality had stronger associations with child DBDs in biological families than adoptive families, indicating the presence of a passive r(GE). Many familial risk factors affected children equally across genetically related and non-related families, providing evidence for direct environmental effects. The relationship of parental antisociality and offspring DBDs was best explained by a passive r(GE), where a general vulnerability toward externalizing psychopathology is passed down by the parents to the children.

  9. European medicinal and edible plants associated with subacute and chronic toxicity part I: Plants with carcinogenic, teratogenic and endocrine-disrupting effects.

    Science.gov (United States)

    Kristanc, Luka; Kreft, Samo

    2016-06-01

    In recent decades, the use of herbal medicines and food products has been widely embraced in many developed countries. These products are generally highly accepted by consumers who often believe that "natural" equals "safe". This is, however, an oversimplification because several botanicals have been found to contain toxic compounds in concentrations harmful to human health. Acutely toxic plants are in most cases already recognised as dangerous as a result of their traditional use, but plants with subacute and chronic toxicity are difficult or even impossible to detect by traditional use or by clinical research studies. In this review, we systematically address major issues including the carcinogenicity, teratogenicity and endocrine-disrupting effects associated with the use of herbal preparations with a strong focus on plant species that either grow natively or are cultivated in Europe. The basic information regarding the molecular mechanisms of the individual subtypes of plant-induced non-acute toxicity is given, which is followed by a discussion of the pathophysiological and clinical characteristics. We describe the genotoxic and carcinogenic effects of alkenylbenzenes, pyrrolizidine alkaloids and bracken fern ptaquiloside, the teratogenicity issues regarding anthraquinone glycosides and specific alkaloids, and discuss the human health concerns regarding the phytoestrogens and licorice consumption in detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells

    Science.gov (United States)

    Yu, Kyeong-Nam; Chang, Seung-Hee; Park, Soo Jin; Lim, Joohyun; Lee, Jinkyu; Yoon, Tae-Jong; Kim, Jun-Sung; Cho, Myung-Haing

    2015-01-01

    Nanomaterials are used in diverse fields including food, cosmetic, and medical industries. Titanium dioxide nanoparticles (TiO2-NP) are widely used, but their effects on biological systems and mechanism of toxicity have not been elucidated fully. Here, we report the toxicological mechanism of TiO2-NP in cell organelles. Human bronchial epithelial cells (16HBE14o-) were exposed to 50 and 100 μg/mL TiO2-NP for 24 and 48 h. Our results showed that TiO2-NP induced endoplasmic reticulum (ER) stress in the cells and disrupted the mitochondria-associated endoplasmic reticulum membranes (MAMs) and calcium ion balance, thereby increasing autophagy. In contrast, an inhibitor of ER stress, tauroursodeoxycholic acid (TUDCA), mitigated the cellular toxic response, suggesting that TiO2-NP promoted toxicity via ER stress. This novel mechanism of TiO2-NP toxicity in human bronchial epithelial cells suggests that further exhaustive research on the harmful effects of these nanoparticles in relevant organisms is needed for their safe application. PMID:26121477

  11. The influence of tomato processing on residues of organochlorine and organophosphate insecticides and their associated dietary risk.

    Science.gov (United States)

    Reiler, Emilie; Jørs, Erik; Bælum, Jesper; Huici, Omar; Alvarez Caero, Maria Mercedes; Cedergreen, Nina

    2015-09-15

    Due to the increasing food demand, the use of pesticides in agriculture is increasing. Particularly in low income countries poor training among farmers, combined with the use of obsolete pesticides may result in a high risk for the consumers. In this study six organochlorines and five organophosphates were analyzed in 54 samples of tomatoes from small scale farmers in Bolivia. The analyses were done on unprocessed, stored, washed and peeled tomatoes. The cumulated risk associated with consumption of the tomatoes after different storage times and processing treatments was evaluated using the Hazard Index (HI) for acute risk assessment. All 11 pesticides were detected in the analyses although several of them are obsolete and included in the Stockholm convention ratified by Bolivia. The organochlorines were found in the μg pesticide/kg tomato range and below the HI, while the organophosphates were present in the mg pesticide/kg tomato range and most often above the HI. The low organochlorine concentrations were not significantly affected by time or treatment, but storage significantly decreased the concentrations of organophosphates. Washing decreased the initial concentrations to between 53% (malathion) down to 2% (ethyl parathion), while peeling had a larger effect reducing the initial concentrations to between 33% (malathion) and 0.7% (chlorpyriphos). Both the acute and chronic cumulative risk assessment of organophosphates showed a dietary risk for unprocessed tomatoes three days after harvest. For children, also the consumption of washed tomatoes constituted a dietary risk. To reduce the dietary risk of pesticide residues in Bolivia, there is an urgent need of farmer education and introduction of less hazardous pesticides as well as resources for surveillance and enforcement of legislation in order to ensure public health. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Residuation theory

    CERN Document Server

    Blyth, T S; Sneddon, I N; Stark, M

    1972-01-01

    Residuation Theory aims to contribute to literature in the field of ordered algebraic structures, especially on the subject of residual mappings. The book is divided into three chapters. Chapter 1 focuses on ordered sets; directed sets; semilattices; lattices; and complete lattices. Chapter 2 tackles Baer rings; Baer semigroups; Foulis semigroups; residual mappings; the notion of involution; and Boolean algebras. Chapter 3 covers residuated groupoids and semigroups; group homomorphic and isotone homomorphic Boolean images of ordered semigroups; Dubreil-Jacotin and Brouwer semigroups; and loli

  13. A disease-associated frameshift mutation in caveolin-1 disrupts caveolae formation and function through introduction of a de novo ER retention signal.

    Science.gov (United States)

    Copeland, Courtney A; Han, Bing; Tiwari, Ajit; Austin, Eric D; Loyd, James E; West, James D; Kenworthy, Anne K

    2017-11-01

    Caveolin-1 (CAV1) is an essential component of caveolae and is implicated in numerous physiological processes. Recent studies have identified heterozygous mutations in the CAV1 gene in patients with pulmonary arterial hypertension (PAH), but the mechanisms by which these mutations impact caveolae assembly and contribute to disease remain unclear. To address this question, we examined the consequences of a familial PAH-associated frameshift mutation in CAV1 , P158PfsX22, on caveolae assembly and function. We show that C-terminus of the CAV1 P158 protein contains a functional ER-retention signal that inhibits ER exit and caveolae formation and accelerates CAV1 turnover in Cav1 -/- MEFs. Moreover, when coexpressed with wild-type (WT) CAV1 in Cav1 -/- MEFs, CAV1-P158 functions as a dominant negative by partially disrupting WT CAV1 trafficking. In patient skin fibroblasts, CAV1 and caveolar accessory protein levels are reduced, fewer caveolae are observed, and CAV1 complexes exhibit biochemical abnormalities. Patient fibroblasts also exhibit decreased resistance to a hypo-osmotic challenge, suggesting the function of caveolae as membrane reservoir is compromised. We conclude that the P158PfsX22 frameshift introduces a gain of function that gives rise to a dominant negative form of CAV1, defining a new mechanism by which disease-associated mutations in CAV1 impair caveolae assembly. © 2017 Copeland, Han, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. Intake of Fruits and Vegetables with Low-to-Moderate Pesticide Residues Is Positively Associated with Semen-Quality Parameters among Young Healthy Men123

    Science.gov (United States)

    Gaskins, Audrey J; Williams, Paige L; Mendiola, Jaime; Levine, Hagai; Hauser, Russ; Swan, Shanna H; Chavarro, Jorge E

    2016-01-01

    Background: Numerous studies have shown that occupational or environmental pesticide exposure can affect male fertility. There is less evidence, however, regarding any potentially adverse effects of pesticide residues in foods on markers of male fertility potential. Objectives: We examined the relations between fruit and vegetable intake, considering pesticide residue status, and semen quality and serum concentrations of reproductive hormones in healthy young men. Methods: The Rochester Young Men's Study is a cross-sectional study that recruited men aged 18–22 y (n = 189) in Rochester, New York. Participants completed a questionnaire, provided a semen sample, had a blood sample drawn, and underwent a physical examination at enrollment. Semen samples were analyzed for total sperm count, sperm concentration, morphology, motility, ejaculate volume, total motile count, and total normal count. Dietary intake during the previous year was assessed by a validated food-frequency questionnaire. Fruit and vegetables were categorized as having high [Pesticide Residue Burden Score (PRBS) ≥4] or low-to-moderate (PRBS vegetable intake with semen variables and reproductive hormones while adjusting for potential confounding factors. Results: The total intake of fruit and vegetables was unrelated to semen quality. However, the intake of fruit and vegetables with low-to-moderate pesticide residues was associated with a higher total sperm count and sperm concentration, whereas the intake of fruit and vegetables with high pesticide residues was unrelated to semen quality. On average, men in the highest quartile of low-to-moderate-pesticide fruit and vegetable intake (≥2.8 servings/d) had a 169% (95% CI: 45%, 400%) higher total sperm count and a 173% (95% CI: 57%, 375%) higher sperm concentration than did men in the lowest quartile (vegetables, regardless of pesticide-residue status, was not associated with reproductive hormone concentrations. Conclusions: The consumption of fruit

  15. Intake of Fruits and Vegetables with Low-to-Moderate Pesticide Residues Is Positively Associated with Semen-Quality Parameters among Young Healthy Men.

    Science.gov (United States)

    Chiu, Yu-Han; Gaskins, Audrey J; Williams, Paige L; Mendiola, Jaime; Jørgensen, Niels; Levine, Hagai; Hauser, Russ; Swan, Shanna H; Chavarro, Jorge E

    2016-05-01

    Numerous studies have shown that occupational or environmental pesticide exposure can affect male fertility. There is less evidence, however, regarding any potentially adverse effects of pesticide residues in foods on markers of male fertility potential. We examined the relations between fruit and vegetable intake, considering pesticide residue status, and semen quality and serum concentrations of reproductive hormones in healthy young men. The Rochester Young Men's Study is a cross-sectional study that recruited men aged 18-22 y (n = 189) in Rochester, New York. Participants completed a questionnaire, provided a semen sample, had a blood sample drawn, and underwent a physical examination at enrollment. Semen samples were analyzed for total sperm count, sperm concentration, morphology, motility, ejaculate volume, total motile count, and total normal count. Dietary intake during the previous year was assessed by a validated food-frequency questionnaire. Fruit and vegetables were categorized as having high [Pesticide Residue Burden Score (PRBS) ≥4] or low-to-moderate (PRBS vegetable intake with semen variables and reproductive hormones while adjusting for potential confounding factors. The total intake of fruit and vegetables was unrelated to semen quality. However, the intake of fruit and vegetables with low-to-moderate pesticide residues was associated with a higher total sperm count and sperm concentration, whereas the intake of fruit and vegetables with high pesticide residues was unrelated to semen quality. On average, men in the highest quartile of low-to-moderate-pesticide fruit and vegetable intake (≥2.8 servings/d) had a 169% (95% CI: 45%, 400%) higher total sperm count and a 173% (95% CI: 57%, 375%) higher sperm concentration than did men in the lowest quartile (vegetables, regardless of pesticide-residue status, was not associated with reproductive hormone concentrations. The consumption of fruit and vegetables with low-to-moderate pesticide residues

  16. Computational characterization of residue couplings and micropolymorphism-induced changes in the dynamics of two differentially disease-associated human MHC class-I alleles.

    Science.gov (United States)

    Serçinoğlu, Onur; Ozbek, Pemra

    2018-02-01

    Human major histocompatibility complex class I (MHC I) - or human leukocyte antigen (HLA) - proteins present intracellularly processed peptides to cytotoxic T lymphocytes in the adaptive immune response to pathogens. A high level of polymorphism in human MHC I proteins defines the peptide-binding specificity of thousands of different MHC alleles. However, polymorphism as well as the peptide ligand can also affect the global dynamics of the complex. In this study, we conducted classical molecular dynamics simulations of two HLA alleles, the ankylosing spondylitis (AS) associated/tapasin-dependent HLA-B*27:05 and nondisease-associated/tapasin-independent HLA-B*27:09, both in peptide-free forms as well as complex with four different peptides ligands. Our results indicate that in peptide-free form, the single amino acid substitution distinguishing the two alleles (D116H), leads to a weaker dynamic coupling of residues in the tapasin-dependent HLA-B*27:05. In peptide-bound form, several residues of the binding-groove, mostly in A and B pockets, show hinge-like behavior in the global motion of the MHC. Moreover, allele-dependent changes are shown in residue interactions, affecting the B-pocket as well as the beta-2-microglobulin (β2m)-facing residues of the HLA chain.

  17. Disruption of metal ion homeostasis in soils is associated with nitrogen deposition-induced species loss in an Inner Mongolia steppe

    Science.gov (United States)

    Tian, Q.-Y.; Liu, N.-N.; Bai, W.-M.; Li, L.-H.; Zhang, W.-H.

    2015-01-01

    Enhanced deposition of atmospheric nitrogen (N) resulting from anthropogenic activities has negative impacts on plant diversity in grassland ecosystems globally. Several mechanisms have been proposed to explain the species loss. Ion toxicity due to N deposition-induced soil acidification has been suggested to be responsible for species loss in acidic grasslands, while few studies have evaluated the role of soil-mediated homeostasis of ions in species loss under elevated N deposition in alkaline grasslands. To determine whether soil-mediated processes are involved in changes in species composition by N deposition, the effects of 9 yr N addition on soil properties, aboveground biomass (AGB) and species composition were investigated in an Inner Mongolia steppe. Low to moderate N addition rate (2, 4, 8 g N m-2 yr-1) significantly enhanced AGB of grasses, while high N addition rate (> 16 g N m-2 yr-1) reduced AGB of forbs, leading to an overall increase in AGB of the community under low to moderate N addition rates. Forb richness was significantly reduced by N addition at rates greater than 8 g N m-2 yr-1, while no effect of N addition on grass richness was observed, resulting in decline in total species richness. N addition depleted base cations (Ca2+, Mg2+ and K+) in soils, reduced soil pH and mobilized Mn2+, Fe3+ and Cu2+ ions in soils. Soil inorganic-N concentration was negatively correlated with forb richness, explaining 27.2% variation of forb richness. The concentrations of base cations (Ca2+ and Mg2+) and metal ions (Mn2+ and Cu2+) showed positively and negatively linear correlation with forb richness, accounting for 25.9 and 41.4% variation of forb richness, respectively. These results reveal that disruption of metal ion homeostasis in soils by N addition, particularly enhanced release of soil Mn2+ and Cu2+ may be associated with reduction in forb richness in temperate steppe of Inner Mongolia.

  18. Malaria-Associated l-Arginine Deficiency Induces Mast Cell-Associated Disruption to Intestinal Barrier Defenses against Nontyphoidal Salmonella Bacteremia

    Science.gov (United States)

    Chau, Jennifer Y.; Tiffany, Caitlin M.; Nimishakavi, Shilpa; Lawrence, Jessica A.; Pakpour, Nazzy; Mooney, Jason P.; Lokken, Kristen L.; Caughey, George H.; Tsolis, Renee M.

    2013-01-01

    Coinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop l-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of l-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive Escherichia coli Nissle and Salmonella enterica serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with l-arginine or l-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with l-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing l-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans. PMID:23690397

  19. Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Inhibits Major Histocompatibility Complex Class II Expression by Disrupting Enhanceosome Assembly through Binding with the Regulatory Factor X Complex.

    Science.gov (United States)

    Thakker, Suhani; Purushothaman, Pravinkumar; Gupta, Namrata; Challa, Shanthan; Cai, Qiliang; Verma, Subhash C

    2015-05-01

    Major histocompatibility complex class II (MHC-II) molecules play a central role in adaptive antiviral immunity by presenting viral peptides to CD4(+) T cells. Due to their key role in adaptive immunity, many viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), have evolved multiple strategies to inhibit the MHC-II antigen presentation pathway. The expression of MHC-II, which is controlled mainly at the level of transcription, is strictly dependent upon the binding of the class II transactivator (CIITA) to the highly conserved promoters of all MHC-II genes. The recruitment of CIITA to MHC-II promoters requires its direct interactions with a preassembled MHC-II enhanceosome consisting of cyclic AMP response element-binding protein (CREB) and nuclear factor Y (NF-Y) complex and regulatory factor X (RFX) complex proteins. Here, we show that KSHV-encoded latency-associated nuclear antigen (LANA) disrupts the association of CIITA with the MHC-II enhanceosome by binding to the components of the RFX complex. Our data show that LANA is capable of binding to all three components of the RFX complex, RFX-associated protein (RFXAP), RFX5, and RFX-associated ankyrin-containing protein (RFXANK), in vivo but binds more strongly with the RFXAP component in in vitro binding assays. Levels of MHC-II proteins were significantly reduced in KSHV-infected as well as LANA-expressing B cells. Additionally, the expression of LANA in a luciferase promoter reporter assay showed reduced HLA-DRA promoter activity in a dose-dependent manner. Chromatin immunoprecipitation assays showed that LANA binds to the MHC-II promoter along with RFX proteins and that the overexpression of LANA disrupts the association of CIITA with the MHC-II promoter. These assays led to the conclusion that the interaction of LANA with RFX proteins interferes with the recruitment of CIITA to MHC-II promoters, resulting in an inhibition of MHC-II gene expression. Thus, the data presented here identify a novel

  20. Residue processing

    Energy Technology Data Exchange (ETDEWEB)

    Gieg, W.; Rank, V.

    1942-10-15

    In the first stage of coal hydrogenation, the liquid phase, light and heavy oils were produced; the latter containing the nonliquefied parts of the coal, the coal ash, and the catalyst substances. It was the problem of residue processing to extract from these so-called let-down oils that which could be used as pasting oils for the coal. The object was to obtain a maximum oil extraction and a complete removal of the solids, because of the latter were returned to the process they would needlessly burden the reaction space. Separation of solids in residue processing could be accomplished by filtration, centrifugation, extraction, distillation, or low-temperature carbonization (L.T.C.). Filtration or centrifugation was most suitable since a maximum oil yield could be expected from it, since only a small portion of the let-down oil contained in the filtration or centrifugation residue had to be thermally treated. The most satisfactory centrifuge at this time was the Laval, which delivered liquid centrifuge residue and centrifuge oil continuously. By comparison, the semi-continuous centrifuges delivered plastic residues which were difficult to handle. Various apparatus such as the spiral screw kiln and the ball kiln were used for low-temperature carbonization of centrifuge residues. Both were based on the idea of carbonization in thin layers. Efforts were also being made to produce electrode carbon and briquette binder as by-products of the liquid coal phase.

  1. ACR/EULAR Definitions of Remission Are Associated with Lower Residual Inflammatory Activity Compared with DAS28 Remission on Hand MRI in Rheumatoid Arthritis.

    Science.gov (United States)

    Lisbona, Maria Pilar; Solano, Albert; Ares, Jesús; Almirall, Miriam; Salman-Monte, Tarek Carlos; Maymó, Joan

    2016-09-01

    To determine the level of residual inflammation [synovitis, bone marrow edema (BME), tenosynovitis, and total inflammation] quantified by hand magnetic resonance imaging (h-MRI) in patients with rheumatoid arthritis (RA) in remission according to 3 different definitions of clinical remission, and to compare these remission definitions. A cross-sectional study. To assess the level of residual MRI inflammation in remission, cutoff levels associated to remission and median scores of MRI residual inflammatory lesions were calculated. Data from an MRI register of patients with RA who have various levels of disease activity were used. These were used for the analyses: synovitis, BME according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system, tenosynovitis, total inflammation, and disease activity composite measures recorded at the time of MRI. Receiver-operating characteristic analysis was used to identify the best cutoffs associated with remission for each inflammatory lesion on h-MRI. Median values of each inflammatory lesion for each definition of remission were also calculated. A total of 388 h-MRI sets of patients with RA with different levels of disease activity, 130 in remission, were included. Cutoff values associated with remission according to the Simplified Disease Activity Index (SDAI) ≤ 3.3 and the Boolean American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) definitions for BME and tenosynovitis (1 and 3, respectively) were lower than BME and tenosynovitis (2 and 5, respectively) for the Disease Activity Score on 28 joints (DAS28) ≤ 2.6. Median scores for synovitis, BME, and total inflammation were also lower for the SDAI and Boolean ACR/EULAR remission criteria compared with DAS28. Patients with RA in remission according to the SDAI and Boolean ACR/EULAR definitions showed lower levels of MRI-detected residual inflammation compared with DAS28.

  2. CATASTROPHIC DISRUPTION OF COMET ISON

    Energy Technology Data Exchange (ETDEWEB)

    Keane, Jacqueline V.; Kleyna, Jan T.; Riesen, Timm-Emmanuel; Meech, Karen J. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Milam, Stefanie N.; Charnley, Steven B. [Astrochemistry Laboratory, NASA GSFC, MS 690, Greenbelt, MD 20771 (United States); Coulson, Iain M. [Joint Astronomy Center, 660 North Aohoku Place, Hilo, HI 96720 (United States); Sekanina, Zdenek [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Kracht, Rainer, E-mail: keane@ifa.hawaii.edu [Ostlandring 53, D-25335 Elmshorn, Schleswig-Holstein (Germany)

    2016-11-10

    We report submillimeter 450 and 850 μ m dust continuum observations for comet C/2012 S1 (ISON) obtained at heliocentric distances 0.31–0.08 au prior to perihelion on 2013 November 28 ( r {sub h} = 0.0125 au). These observations reveal a rapidly varying dust environment in which the dust emission was initially point-like. As ISON approached perihelion, the continuum emission became an elongated dust column spread out over as much as 60″ (>10{sup 5} km) in the anti-solar direction. Deconvolution of the November 28.04 850 μ m image reveals numerous distinct clumps consistent with the catastrophic disruption of comet ISON, producing ∼5.2 × 10{sup 10} kg of submillimeter-sized dust. Orbital computations suggest that the SCUBA-2 emission peak coincides with the comet's residual nucleus.

  3. Catastrophic Disruption of Comet ISON

    Science.gov (United States)

    Keane, Jacqueline V.; Milam, Stefanie N.; Coulson, Iain M.; Kleyna, Jan T.; Sekanina, Zdenek; Kracht, Rainer; Riesen, Timm-Emmanuel; Meech, Karen J.; Charnley, Steven B.

    2016-01-01

    We report submillimeter 450 and 850 microns dust continuum observations for comet C/2012 S1 (ISON) obtained at heliocentric distances 0.31-0.08 au prior to perihelion on 2013 November 28 (rh?=?0.0125 au). These observations reveal a rapidly varying dust environment in which the dust emission was initially point-like. As ISON approached perihelion, the continuum emission became an elongated dust column spread out over as much as 60? (greater than 10(exp 5) km in the anti-solar direction. Deconvolution of the November 28.04 850 microns image reveals numerous distinct clumps consistent with the catastrophic disruption of comet ISON, producing approximately 5.2?×?10(exp 10) kg of submillimeter-sized dust. Orbital computations suggest that the SCUBA-2 emission peak coincides with the comet's residual nucleus.

  4. Disruptions, disruptivity and safer operating windows in the high-β spherical torus NSTX

    International Nuclear Information System (INIS)

    Gerhardt, S.P.; Bell, R.E.; Diallo, A.; Gates, D.; LeBlanc, B.P.; Menard, J.E.; Mueller, D.; Sabbagh, S.A.; Soukhanovskii, V.; Tritz, K.; Yuh, H.

    2013-01-01

    This paper discusses disruption rates, disruption causes and disruptivity statistics in the high-β N National Spherical Torus Experiment (NSTX) (Ono et al 2000 Nucl. Fusion 40 557). While the overall disruption rate is rather high, configurations with high β N , moderate q * , strong boundary shaping, sufficient rotation and broad pressure and current profiles are found to have the lowest disruptivity; active n = 1 control further reduces the disruptivity. The disruptivity increases rapidly for q * min > 1.25 is generally acceptable for avoiding the onset of core rotating n = 1 kink/tearing modes; when EPM and ELM disturbances are present, the required q min for avoiding those modes is raised to ∼1.5. The current ramp and early flat-top phase of the discharges are prone to n = 1 core rotating modes locking to the wall, leading to a disruption. Small changes to the discharge fuelling during this phase can often mitigate the rotation damping associated with these modes and eliminate the disruption. The largest stored-energy disruptions are those that occur at high current when a plasma current ramp-down is initiated incorrectly. (paper)

  5. Handling of Solid Residues

    International Nuclear Information System (INIS)

    Medina Bermudez, Clara Ines

    1999-01-01

    The topic of solid residues is specifically of great interest and concern for the authorities, institutions and community that identify in them a true threat against the human health and the atmosphere in the related with the aesthetic deterioration of the urban centers and of the natural landscape; in the proliferation of vectorial transmitters of illnesses and the effect on the biodiversity. Inside the wide spectrum of topics that they keep relationship with the environmental protection, the inadequate handling of solid residues and residues dangerous squatter an important line in the definition of political and practical environmentally sustainable. The industrial development and the population's growth have originated a continuous increase in the production of solid residues; of equal it forms, their composition day after day is more heterogeneous. The base for the good handling includes the appropriate intervention of the different stages of an integral administration of residues, which include the separation in the source, the gathering, the handling, the use, treatment, final disposition and the institutional organization of the administration. The topic of the dangerous residues generates more expectation. These residues understand from those of pathogen type that are generated in the establishments of health that of hospital attention, until those of combustible, inflammable type, explosive, radio-active, volatile, corrosive, reagent or toxic, associated to numerous industrial processes, common in our countries in development

  6. Two nuclear export signals of Cdc6 are differentially associated with CDK-mediated phosphorylation residues for cytoplasmic translocation.

    Science.gov (United States)

    Hwang, In Sun; Woo, Sang Uk; Park, Ji-Woong; Lee, Seung Ki; Yim, Hyungshin

    2014-02-01

    Cdc6 is cleaved at residues 442 and 290 by caspase-3 during apoptosis producing p49-tCdc6 and p32-tCdc6, respectively. While p32-tCdc6 is unable to translocate into the cytoplasm, p49-tCdc6 retains cytoplasmic translocation activity, but it has a lower efficiency than wild-type Cdc6. We hypothesized that a novel nuclear export signal (NES) sequence exists between amino acids 290 and 442. Cdc6 contains a novel NES in the region of amino acids 300-315 (NES2) that shares sequence similarity with NES1 at residues 462-476. In mutant versions of Cdc6, we replaced leucine with alanine in NES1 and NES2 and co-expressed the mutant constructs with cyclin A. We observed that the cytoplasmic translocation of these mutants was reduced in comparison to wild-type Cdc6. Moreover, the cytoplasmic translocation of a mutant in which all four leucine residues were mutated to alanine was significantly inhibited in comparison to the translocation of wild-type Cdc6. The Crm1 binding activities of Cdc6 NES mutants were consistent with the efficiency of its cytoplasmic translocation. Further studies have revealed that L468 and L470 of NES1 are required for cytoplasmic translocation of Cdc6 phosphorylated at S74, while L311 and L313 of NES2 accelerate the cytoplasmic translocation of Cdc6 phosphorylated at S54. These results suggest that the two NESs of Cdc6 work cooperatively and distinctly for the cytoplasmic translocation of Cdc6 phosphorylated at S74 and S54 by cyclin A/Cdk2. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Identification of HLA-DQalpha and -DRbeta residues associated with susceptibility and protection to epithelial ovarian cancer.

    Science.gov (United States)

    Monos, Dimitri S; Pappas, John; Magira, Eleni E; Gaughan, John; Aplenc, Richard; Sakkas, Lazaros; Freedman, Ralph; Reveille, John D; Platsoucas, Chris D

    2005-05-01

    Substantial evidence has been accumulated suggesting that T cells in patients with epithelial ovarian carcinoma (EOC) exhibit an antigen-driven immune response directed against the tumor cells. In the context of human leukocyte antigen (HLA), this suggests its possible involvement in the disease. Therefore, we examined the distribution of the HLA-DRB1*, -DQA1*, and -DQB1* alleles in 47 patients with EOC and 67 healthy Caucasian women. The frequency of D(70) and E(71) polymorphic residues of the DRB1 alleles was significantly reduced in EOC patients versus controls (pD(70)E(71) = 0.009), suggesting a protective role against the disease. The DQalpha residues R(52) and Y(11)R(55) were increased in the patients (p = 0.008 and 0.012, respectively). Because residues 11 and 55 participate in the formation of pocket 1, they may be functionally important amino acid positions that influence disease susceptibility. The frequency of the DQalpha susceptibility epitope (R(52)Y(11)R(55)) among the DRbetaD(70)E(71)-positive EOC patients was increased when compared with DRbetaD(70)E(71)-positive controls (EOC, 100%; control, 52%; p = 0.028). Among individuals without the DQalpha susceptibility epitope, the distribution of DRbetaD(70)E(71)-positive cases was significantly different between EOC patients and controls (EOC, 0%; control, 60%; p = 0.039). Therefore, it appears that the presence of DQalpha susceptibility elements overrides the protective effect of the DRbetaD(70)E(71) epitope and suggests an interactive relationship between DRbeta and DQalpha epitopes that may be of importance for disease susceptibility. Because positions DRbeta 70,71 and DQalpha 52 have been implicated in immunologic diseases, it is likely that besides being critical for T-cell recognition, they may also play a role in T-cell development and acquisition of the T-cell repertoire.

  8. Impact of single annual treatment and four-monthly treatment for hookworm and Ascaris lumbricoides, and factors associated with residual infection among Kenyan school children.

    Science.gov (United States)

    Kepha, Stella; Mwandawiro, Charles S; Anderson, Roy M; Pullan, Rachel L; Nuwaha, Fred; Cano, Jorge; Njenga, Sammy M; Odiere, Maurice R; Allen, Elizabeth; Brooker, Simon J; Nikolay, Birgit

    2017-02-09

    School-based deworming is widely implemented in various countries to reduce the burden of soil-transmitted helminths (STHs), however, the frequency of drug administration varies in different settings. In this study, we compared the impact of a single annual treatment and 4-monthly treatment over a follow-up among Kenyan school children, and investigated the factors associated with residual infection. We performed a secondary analysis of data from a randomized trial investigating whether deworming for STHs alters risk of acquiring malaria. Children received either a single treatment or 4-monthly albendazole treatments were followed longitudinally from February 2014 to October 2014. The relative impact of treatment and factors associated with residual infections were investigated using mixed-effects regression models. Predisposition to infection was assessed based on Spearman's rank and Kendall's Tau correlation coefficients. In the 4-monthly treatment group, the proportion of children infected with hookworm decreased from 59.9 to 5.7%, while Ascaris lumbricoides infections dropped from 55.7 to 6.2%. In the single treatment group, hookworm infections decreased over the same time period from 58.7 to 18.3% (12.6% absolute difference in reduction, 95% CI: 8.9-16.3%), and A. lumbricoides from 56.7 to 23.3% (17.1% absolute difference in reduction, 95% CI: 13.1-21.1%). There was strong evidence for predisposition to both STH types. Residual hookworm infection among children on 4-monthly treatment were associated with male sex and baseline nutritional status, whereas A. lumbricoides infection was associated with individual and school-level infection at baseline, latrine cleanliness at schools. This study found that 4-monthly treatment w more effective than single annual treatment. Repeated treatments led to dramatic reductions in the intensities of STHs, but did not completely clear infections among school children in Kenya, a presumed reflection of reinfection in a setting

  9. Longitudinal associations between maternal disrupted representations, maternal interactive behavior and infant attachment: a comparison between full-term and preterm dyads.

    Science.gov (United States)

    Hall, R A S; Hoffenkamp, H N; Tooten, A; Braeken, J; Vingerhoets, A J J M; van Bakel, H J A

    2015-04-01

    This prospective study examined whether or not a mother's representations of her infant were more often disrupted after premature childbirth. Furthermore, the study examined if different components of maternal interactive behavior mediated the relation between maternal disrupted representations and infant attachment. The participants were mothers of full-term (n = 75), moderately preterm (n = 68) and very preterm infants (n = 67). Maternal representations were assessed by the Working Model of the Child Interview at 6 months post-partum. Maternal interactive behavior was evaluated at 6 and 24 months post-partum, using the National Institute of Child Health and Human Development Early Care Research Network mother-infant observation scales. Infant attachment was observed at 24 months post-partum and was coded by the Attachment Q-Set. The results reveal that a premature childbirth does not necessarily generate disrupted maternal representations of the infant. Furthermore, maternal interactive behavior appears to be an important mechanism through which maternal representations influence the development of infant attachment in full-term and preterm infants. Early assessment of maternal representations can identify mother-infant dyads at risk, in full-term and preterm samples.

  10. Search and Disrupt

    DEFF Research Database (Denmark)

    Ørding Olsen, Anders

    Extant research on external knowledge search and open innovation assumes that collaborators are aligned in their strategic interests towards solving innovation problems. However, disruptive innovation is known to threaten the competitive advantage of incumbent firms, thereby creating a potential...

  11. Search and Disrupt

    DEFF Research Database (Denmark)

    Ørding Olsen, Anders

    This paper analyzes how external search is affected by strategic interest alignment among knowledge sources. I focus on misalignment arising from the heterogeneous effects of disruptive technologies by analyzing the influence of incumbents on 2,855 non-incumbents? external knowledge search efforts....... The efforts most likely to solve innovation problems obtained funding from the European Commission?s 7th Framework Program (2007-2013). The results show that involving incumbents improves search in complementary technologies, while demoting it when strategic interests are misaligned in disruptive technologies....... However, incumbent sources engaged in capability reconfiguration to accommodate disruption improve search efforts in disruptive technologies. The paper concludes that the value of external sources is contingent on more than their knowledge. Specifically, interdependence of sources in search gives rise...

  12. Disruption Rose Tinted II

    OpenAIRE

    Livingstone, Andrew

    2009-01-01

    'Disruption - Rose Tinted II' continues to engage narratives of historical English china as previously explored in the work 'Rose Tinted'. This work engages the sleepy rural idyll which is overlaid with visual contemporary social commentary.

  13. Digital disruption ?syndromes.

    Science.gov (United States)

    Sullivan, Clair; Staib, Andrew

    2017-05-18

    The digital transformation of hospitals in Australia is occurring rapidly in order to facilitate innovation and improve efficiency. Rapid transformation can cause temporary disruption of hospital workflows and staff as processes are adapted to the new digital workflows. The aim of this paper is to outline various types of digital disruption and some strategies for effective management. A large tertiary university hospital recently underwent a rapid, successful roll-out of an integrated electronic medical record (EMR). We observed this transformation and propose several digital disruption "syndromes" to assist with understanding and management during digital transformation: digital deceleration, digital transparency, digital hypervigilance, data discordance, digital churn and post-digital 'depression'. These 'syndromes' are defined and discussed in detail. Successful management of this temporary digital disruption is important to ensure a successful transition to a digital platform. What is known about this topic? Digital disruption is defined as the changes facilitated by digital technologies that occur at a pace and magnitude that disrupt established ways of value creation, social interactions, doing business and more generally our thinking. Increasing numbers of Australian hospitals are implementing digital solutions to replace traditional paper-based systems for patient care in order to create opportunities for improved care and efficiencies. Such large scale change has the potential to create transient disruption to workflows and staff. Managing this temporary disruption effectively is an important factor in the successful implementation of an EMR. What does this paper add? A large tertiary university hospital recently underwent a successful rapid roll-out of an integrated electronic medical record (EMR) to become Australia's largest digital hospital over a 3-week period. We observed and assisted with the management of several cultural, behavioural and

  14. Endocrine disrupting compounds

    DEFF Research Database (Denmark)

    Bøgh, I B; Christensen, P; Dantzer, V

    2001-01-01

    processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...... or embryo models for the evaluation of possible consequences of human exposure to endocrine disrupting compounds is discussed. Furthermore, possible consequences of exposure to endocrine disrupting compounds for the embryo transfer industry are addressed....

  15. Disruptive Mood Dysregulation Disorder (DMDD)

    Science.gov (United States)

    ... for Families Guide Facts for Families - Vietnamese Disruptive Mood Dysregulation Disorder (DMDD) No. 110; Updated May 2013 Disruptive Mood Dysregulation Disorder (DMDD) is a relatively new diagnosis ...

  16. Residual risk

    African Journals Online (AJOL)

    ing the residual risk of transmission of HIV by blood transfusion. An epidemiological approach assumed that all HIV infections detected serologically in first-time donors were pre-existing or prevalent infections, and that all infections detected in repeat blood donors were new or incident infections. During 1986 - 1987,0,012%.

  17. ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins.

    Science.gov (United States)

    de Castro, Edouard; Sigrist, Christian J A; Gattiker, Alexandre; Bulliard, Virginie; Langendijk-Genevaux, Petra S; Gasteiger, Elisabeth; Bairoch, Amos; Hulo, Nicolas

    2006-07-01

    ScanProsite--http://www.expasy.org/tools/scanprosite/--is a new and improved version of the web-based tool for detecting PROSITE signature matches in protein sequences. For a number of PROSITE profiles, the tool now makes use of ProRules--context-dependent annotation templates--to detect functional and structural intra-domain residues. The detection of those features enhances the power of function prediction based on profiles. Both user-defined sequences and sequences from the UniProt Knowledgebase can be matched against custom patterns, or against PROSITE signatures. To improve response times, matches of sequences from UniProtKB against PROSITE signatures are now retrieved from a pre-computed match database. Several output modes are available including simple text views and a rich mode providing an interactive match and feature viewer with a graphical representation of results.

  18. The leading mode of observed and CMIP5 ENSO-residual sea surface temperatures and associated changes in Indo-Pacific climate

    Science.gov (United States)

    Funk, Christopher C.; Hoell. Andrew,

    2015-01-01

    SSTs in the western Pacific Ocean have tracked closely with CMIP5 simulations despite recent hiatus cooling in the eastern Pacific. This paper quantifies these similarities and associated circulation and precipitation variations using the first global 1900–2012 ENSO-residual empirical orthogonal functions (EOFs) of 35 variables: observed SSTs; 28 CMIP5 SST simulations; Simple Ocean Data Assimilation (SODA) 25-, 70-, and 171-m ocean temperatures and sea surface heights (SSHs); and Twentieth Century Reanalysis, version 2 (20CRv2), surface winds and precipitation.

  19. Disruption prediction at JET

    International Nuclear Information System (INIS)

    Milani, F.

    1998-12-01

    The sudden loss of the plasma magnetic confinement, known as disruption, is one of the major issue in a nuclear fusion machine as JET (Joint European Torus). Disruptions pose very serious problems to the safety of the machine. The energy stored in the plasma is released to the machine structure in few milliseconds resulting in forces that at JET reach several Mega Newtons. The problem is even more severe in the nuclear fusion power station where the forces are in the order of one hundred Mega Newtons. The events that occur during a disruption are still not well understood even if some mechanisms that can lead to a disruption have been identified and can be used to predict them. Unfortunately it is always a combination of these events that generates a disruption and therefore it is not possible to use simple algorithms to predict it. This thesis analyses the possibility of using neural network algorithms to predict plasma disruptions in real time. This involves the determination of plasma parameters every few milliseconds. A plasma boundary reconstruction algorithm, XLOC, has been developed in collaboration with Dr. D. O'Brien and Dr. J. Ellis capable of determining the plasma wall/distance every 2 milliseconds. The XLOC output has been used to develop a multilayer perceptron network to determine plasma parameters as l i and q ψ with which a machine operational space has been experimentally defined. If the limits of this operational space are breached the disruption probability increases considerably. Another approach for prediction disruptions is to use neural network classification methods to define the JET operational space. Two methods have been studied. The first method uses a multilayer perceptron network with softmax activation function for the output layer. This method can be used for classifying the input patterns in various classes. In this case the plasma input patterns have been divided between disrupting and safe patterns, giving the possibility of

  20. Residual basins

    International Nuclear Information System (INIS)

    D'Elboux, C.V.; Paiva, I.B.

    1980-01-01

    Exploration for uranium carried out over a major portion of the Rio Grande do Sul Shield has revealed a number of small residual basins developed along glacially eroded channels of pre-Permian age. Mineralization of uranium occurs in two distinct sedimentary units. The lower unit consists of rhythmites overlain by a sequence of black shales, siltstones and coal seams, while the upper one is dominated by sandstones of probable fluvial origin. (Author) [pt

  1. Fat residue and use-wear found on Acheulian biface and scraper associated with butchered elephant remains at the site of Revadim, Israel.

    Directory of Open Access Journals (Sweden)

    Natalya Solodenko

    Full Text Available The archaeological record indicates that elephants must have played a significant role in early human diet and culture during Palaeolithic times in the Old World. However, the nature of interactions between early humans and elephants is still under discussion. Elephant remains are found in Palaeolithic sites, both open-air and cave sites, in Europe, Asia, the Levant, and Africa. In some cases elephant and mammoth remains indicate evidence for butchering and marrow extraction performed by humans. Revadim Quarry (Israel is a Late Acheulian site where elephant remains were found in association with characteristic Lower Palaeolithic flint tools. In this paper we present results regarding the use of Palaeolithic tools in processing animal carcasses and rare identification of fat residue preserved on Lower Palaeolithic tools. Our results shed new light on the use of Palaeolithic stone tools and provide, for the first time, direct evidence (residue of animal exploitation through the use of an Acheulian biface and a scraper. The association of an elephant rib bearing cut marks with these tools may reinforce the view suggesting the use of Palaeolithic stone tools in the consumption of large game.

  2. Detection of antibiotic residues and association of cefquinome residues with the occurrence of Extended-Spectrum β-Lactamase (ESBL)-producing bacteria in waste milk samples from dairy farms in England and Wales in 2011.

    Science.gov (United States)

    Randall, Luke; Heinrich, Katharina; Horton, Robert; Brunton, Lucy; Sharman, Matthew; Bailey-Horne, Victoria; Sharma, Meenaxi; McLaren, Ian; Coldham, Nick; Teale, Chris; Jones, Jeff

    2014-02-01

    Waste milk samples from 103 farms in England and Wales were examined for the presence of β-lactam antibiotics and ESBL-producing Enterobacteriaceae. Approximately 10 months after the initial sampling, further waste milk, environmental and faecal samples from farms shown to be positive for CTX-M Escherichia coli were investigated further. Isolates with an ESBL phenotype were tested by PCR for the presence of blaCTX-M, blaOXA, blaSHV and blaTEM genes. Isolates positive for blaCTX-M were sequenced to determine CTX-M type. Representative isolates were further examined by PFGE, plasmid replicon typing and serotyping. Of particular interest, 21.4% of waste milk samples contained residues of the cephalosporin cefquinome, which was significantly associated with CTX-M bacteria. Such bacteria occurred in 5.8% of the waste milk samples (including 3.9% CTX-M E. coli). CTX-M types identified were 1, 14, 14b and 15, but none of the E. coli were serotype O25, the serotype of the human pandemic strain. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  3. Emerging and Disruptive Technologies.

    Science.gov (United States)

    Kricka, Larry J

    2016-08-01

    Several emerging or disruptive technologies can be identified that might, at some point in the future, displace established laboratory medicine technologies and practices. These include increased automation in the form of robots, 3-D printing, technology convergence (e.g., plug-in glucose meters for smart phones), new point-of-care technologies (e.g., contact lenses with sensors, digital and wireless enabled pregnancy tests) and testing locations (e.g., Retail Health Clinics, new at-home testing formats), new types of specimens (e.g., cell free DNA), big biology/data (e.g., million genome projects), and new regulations (e.g., for laboratory developed tests). In addition, there are many emerging technologies (e.g., planar arrays, mass spectrometry) that might find even broader application in the future and therefore also disrupt current practice. One interesting source of disruptive technology may prove to be the Qualcomm Tricorder XPrize, currently in its final stages.

  4. Interruptions disrupt reading comprehension.

    Science.gov (United States)

    Foroughi, Cyrus K; Werner, Nicole E; Barragán, Daniela; Boehm-Davis, Deborah A

    2015-06-01

    Previous research suggests that being interrupted while reading a text does not disrupt the later recognition or recall of information from that text. This research is used as support for Ericsson and Kintsch's (1995) long-term working memory (LT-WM) theory, which posits that disruptions while reading (e.g., interruptions) do not impair subsequent text comprehension. However, to fully comprehend a text, individuals may need to do more than recognize or recall information that has been presented in the text at a later time. Reading comprehension often requires individuals to connect and synthesize information across a text (e.g., successfully identifying complex topics such as themes and tones) and not just make a familiarity-based decision (i.e., recognition). The goal for this study was to determine whether interruptions while reading disrupt reading comprehension when the questions assessing comprehension require participants to connect and synthesize information across the passage. In Experiment 1, interruptions disrupted reading comprehension. In Experiment 2, interruptions disrupted reading comprehension but not recognition of information from the text. In Experiment 3, the addition of a 15-s time-out prior to the interruption successfully removed these negative effects. These data suggest that the time it takes to process the information needed to successfully comprehend text when reading is greater than that required for recognition. Any interference (e.g., an interruption) that occurs during the comprehension process may disrupt reading comprehension. This evidence supports the need for transient activation of information in working memory for successful text comprehension and does not support LT-WM theory. (c) 2015 APA, all rights reserved).

  5. Towards a Framework of Digital Platform Disruption

    DEFF Research Database (Denmark)

    Kazan, Erol; Tan, Chee-Wee; Lim, Eric T. K.

    2014-01-01

    Digital platforms are disruptive information technology (IT) artifacts that erode conventional business logic associated with traditional market structures. This paper presents a framework for examining the disruptive potential of digital platforms whereby we postulate that the strategic interplay...... of governance regimes and platform layers is deterministic of whether disruptive derivatives are permitted to flourish. This framework has been employed in a comparative case study between centralized (i.e., PayPal) and decentralized (i.e., Coinkite) digital payment platforms to illustrate its applicability...... and yield propositions on the nature and impact of digital platform disruptions. Preliminary findings indicate that centralized digital platforms attempt to create unique configurals to obtain monopolistic power by tightly coupling platform layers, which are difficult to replicate. Conversely, decentralized...

  6. A large-scale association study for nanoparticle C60 uncovers mechanisms of nanotoxicity disrupting the native conformations of DNA/RNA.

    Science.gov (United States)

    Xu, Xue; Wang, Xia; Li, Yan; Wang, Yonghua; Yang, Ling

    2012-09-01

    Nano-scale particles have attracted a lot of attention for its potential use in medical studies, in particular for the diagnostic and therapeutic purposes. However, the toxicity and other side effects caused by the undesired interaction between nanoparticles and DNA/RNA are not clear. To address this problem, a model to evaluate the general rules governing how nanoparticles interact with DNA/RNA is demanded. Here by, use of an examination of 2254 native nucleotides with molecular dynamics simulation and thermodynamic analysis, we demonstrate how the DNA/RNA native structures are disrupted by the fullerene (C60) in a physiological condition. The nanoparticle was found to bind with the minor grooves of double-stranded DNA and trigger unwinding and disrupting of the DNA helix, which indicates C60 can potentially inhibit the DNA replication and induce potential side effects. In contrast to that of DNA, C60 only binds to the major grooves of RNA helix, which stabilizes the RNA structure or transforms the configuration from stretch to curl. This finding sheds new light on how C60 inhibits reverse transcription as HIV replicates. In addition, the binding of C60 stabilizes the structures of RNA riboswitch, indicating that C60 might regulate the gene expression. The binding energies of C60 with different genomic fragments varies in the range of -56 to -10 kcal mol(-1), which further verifies the role of nanoparticle in DNA/RNA damage. Our findings reveal a general mode by which C60 causes DNA/RNA damage or other toxic effects at a systematic level, suggesting it should be cautious to handle these nanomaterials in various medical applications.

  7. Heating oil, distillates and residuals outlook

    International Nuclear Information System (INIS)

    Ervin, M.J.

    2004-01-01

    M.J. Ervin and Associates offers strategic planning support to the downstream petroleum industry in terms of price market monitoring, market analysis, media commentary and benchmarking of marketing operations. This presentation included graphs depicting supply and demand for heating oil distillates and residuals from the mid 1990s to 2004. It was noted that the long-term decline in residuals demand in the United States and Canada are due to environmental issues, the use of natural gas as an alternative, and the increasing complexity of refineries. Graphs depicting market impacts of refinery utilization and inventory trends showed that middle distillate production will increase at the expense of gasoline production. Middle distillates and gasoline markets will be more sensitive to supply disruptions, resulting in more frequent price spikes. Inventory trends indicate a greater reliance on product imports. The demand for heating fuel has stabilized due to the continued penetration of natural gas in eastern states and provinces. The demand for diesel fuel has growth 1.5 to 2 per cent while the demand for jet fuel has remained relatively flat and depends greatly on the growth of the gross national product (GNP). tabs., figs

  8. Managing Supply Chain Disruptions

    Science.gov (United States)

    2008-08-09

    additional resources such as increased levels of inventory to restore operations following a disruption (Stonebraker & Afifi , 2004; Zsidisin et al...Other Disciplines to Logistics. International Journal of Physical Distribution & Logistics Management, 27(9/10), pp 515. Stonebraker, P. W. & Afifi

  9. Sustainable Disruption Management

    DEFF Research Database (Denmark)

    Vaaben, Bo Valdemar

    when managing recovery from disruptions. The underlying work of this thesis is carried out as an industrial PhD project in co-operation with the company Jeppesen, which have the airline industry as its primary area of business and the maritime industry as its secondary area. For this reason the thesis...

  10. Fisheries-induced disruptive selection.

    Science.gov (United States)

    Landi, Pietro; Hui, Cang; Dieckmann, Ulf

    2015-01-21

    Commercial harvesting is recognized to induce adaptive responses of life-history traits in fish populations, in particular by shifting the age and size at maturation through directional selection. In addition to such evolution of a target stock, the corresponding fishery itself may adapt, in terms of fishing policy, technological progress, fleet dynamics, and adaptive harvest. The aim of this study is to assess how the interplay between natural and artificial selection, in the simplest setting in which a fishery and a target stock coevolve, can lead to disruptive selection, which in turn may cause trait diversification. To this end, we build an eco-evolutionary model for a size-structured population, in which both the stock׳s maturation schedule and the fishery׳s harvest rate are adaptive, while fishing may be subject to a selective policy based on fish size and/or maturity stage. Using numerical bifurcation analysis, we study how the potential for disruptive selection changes with fishing policy, fishing mortality, harvest specialization, life-history tradeoffs associated with early maturation, and other demographic and environmental parameters. We report the following findings. First, fisheries-induced disruptive selection is readily caused by commonly used fishing policies, and occurs even for policies that are not specific for fish size or maturity, provided that the harvest is sufficiently adaptive and large individuals are targeted intensively. Second, disruptive selection is more likely in stocks in which the selective pressure for early maturation is naturally strong, provided life-history tradeoffs are sufficiently consequential. Third, when a fish stock is overexploited, fisheries targeting only large individuals might slightly increase sustainable yield by causing trait diversification (even though the resultant yield always remains lower than the maximum sustainable yield that could be obtained under low fishing mortality, without causing disruptive

  11. Development of Disruptive Open Access Journals

    Science.gov (United States)

    Anderson, Terry; McConkey, Brigette

    2009-01-01

    Open access (OA) publication has emerged, with disruptive effects, as a major outlet for scholarly publication. OA publication is usually associated with on-line distribution and provides access to scholarly publications to anyone, anywhere--regardless of their ability to pay subscription fees or their association with an educational institution.…

  12. Carbon emissions associated with the procurement and utilization of forest harvest residues for energy, northern Minnesota, USA

    Science.gov (United States)

    Grant M. Domke; Dennis R. Becker; Anthony W. D' Amato; Alan R. Ek; Christopher W. Woodall

    2012-01-01

    Interest in the use of forest-derived biomass for energy has prompted comparisons to fossil fuels and led to controversy over the atmospheric consequences of its utilization. Much of the debate has centered on the carbon storage implications of utilizing whole trees for energy and the time frame necessary to offset the carbon emissions associated with fixed-life...

  13. Statistical analysis of JET disruptions

    International Nuclear Information System (INIS)

    Tanga, A.; Johnson, M.F.

    1991-07-01

    In the operation of JET and of any tokamak many discharges are terminated by a major disruption. The disruptive termination of a discharge is usually an unwanted event which may cause damage to the structure of the vessel. In a reactor disruptions are potentially a very serious problem, hence the importance of studying them and devising methods to avoid disruptions. Statistical information has been collected about the disruptions which have occurred at JET over a long span of operations. The analysis is focused on the operational aspects of the disruptions rather than on the underlining physics. (Author)

  14. An Ecological Perspective on Sleep Disruption.

    Science.gov (United States)

    Tougeron, Kévin; Abram, Paul K

    2017-09-01

    Despite its evolutionary importance and apparent ubiquity among animals, the ecological significance of sleep is largely unresolved. The ecology of sleep has been particularly neglected in invertebrates. In insects, recent neurobehavioral research convincingly demonstrates that resting behavior shares several common characteristics with sleep in vertebrates. Laboratory studies have produced compelling evidence that sleep disruption can cause changes in insect daily activity patterns (via "sleep rebound") and have consequences for behavioral performance during active periods. However, factors that could cause insect sleep disruption in nature have not been considered nor have the ecological consequences. Drawing on evidence from laboratory studies, we argue that sleep disruption may be an overlooked component of insect ecology and could be caused by a variety of anthropogenic and nonanthropogenic factors in nature. We identify several candidate sleep-disrupting factors and provide new insights on the potential consequences of sleep disruption on individual fitness, species interactions, and ecosystem services. We propose an experimental framework to bridge the current gap in knowledge between laboratory and field studies. We conclude that sleep disruption is a potential mechanism underpinning variation in behavioral, population, and community-level processes associated with several aspects of global change.

  15. RESIDUAL RISK ASSESSMENTS - RESIDUAL RISK ...

    Science.gov (United States)

    This source category previously subjected to a technology-based standard will be examined to determine if health or ecological risks are significant enough to warrant further regulation for Coke Ovens. These assesments utilize existing models and data bases to examine the multi-media and multi-pollutant impacts of air toxics emissions on human health and the environment. Details on the assessment process and methodologies can be found in EPA's Residual Risk Report to Congress issued in March of 1999 (see web site). To assess the health risks imposed by air toxics emissions from Coke Ovens to determine if control technology standards previously established are adequately protecting public health.

  16. A Cysteine-Rich Protein Kinase Associates with a Membrane Immune Complex and the Cysteine Residues Are Required for Cell Death.

    Science.gov (United States)

    Yadeta, Koste A; Elmore, James M; Creer, Athena Y; Feng, Baomin; Franco, Jessica Y; Rufian, Jose Sebastian; He, Ping; Phinney, Brett; Coaker, Gitta

    2017-01-01

    Membrane-localized proteins perceive and respond to biotic and abiotic stresses. We performed quantitative proteomics on plasma membrane-enriched samples from Arabidopsis (Arabidopsis thaliana) treated with bacterial flagellin. We identified multiple receptor-like protein kinases changing in abundance, including cysteine (Cys)-rich receptor-like kinases (CRKs) that are up-regulated upon the perception of flagellin. CRKs possess extracellular Cys-rich domains and constitute a gene family consisting of 46 members in Arabidopsis. The single transfer DNA insertion lines CRK28 and CRK29, two CRKs induced in response to flagellin perception, did not exhibit robust alterations in immune responses. In contrast, silencing of multiple bacterial flagellin-induced CRKs resulted in enhanced susceptibility to pathogenic Pseudomonas syringae, indicating functional redundancy in this large gene family. Enhanced expression of CRK28 in Arabidopsis increased disease resistance to P. syringae Expression of CRK28 in Nicotiana benthamiana induced cell death, which required intact extracellular Cys residues and a conserved kinase active site. CRK28-mediated cell death required the common receptor-like protein kinase coreceptor BAK1. CRK28 associated with BAK1 as well as the activated FLAGELLIN-SENSING2 (FLS2) immune receptor complex. CRK28 self-associated as well as associated with the closely related CRK29. These data support a model where Arabidopsis CRKs are synthesized upon pathogen perception, associate with the FLS2 complex, and coordinately act to enhance plant immune responses. © 2017 American Society of Plant Biologists. All Rights Reserved.

  17. Allosteric Inhibition Through Core Disruption

    Energy Technology Data Exchange (ETDEWEB)

    Horn, James R.; Shoichet, Brian K. (NWU); (UCSF)

    2010-03-05

    Although inhibitors typically bind pre-formed sites on proteins, it is theoretically possible to inhibit by disrupting the folded structure of a protein or, in the limit, to bind preferentially to the unfolded state. Equilibria defining how such molecules act are well understood, but structural models for such binding are unknown. Two novel inhibitors of {beta}-lactamase were found to destabilize the enzyme at high temperatures, but at lower temperatures showed no preference for destabilized mutant enzymes versus stabilized mutants. X-ray crystal structures showed that both inhibitors bound to a cryptic site in {beta}-lactamase, which the inhibitors themselves created by forcing apart helixes 11 and 12. This opened up a portion of the hydrophobic core of the protein, into which these two inhibitors bind. Although this binding site is 16 {angstrom} from the center of the active site, the conformational changes were transmitted through a sequence of linked motions to a key catalytic residue, Arg244, which in the complex adopts conformations very different from those in catalytically competent enzyme conformations. These structures offer a detailed view of what has heretofore been a theoretical construct, and suggest the possibility for further design against this novel site.

  18. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

    Directory of Open Access Journals (Sweden)

    Duy Ngoc Do

    2014-09-01

    Full Text Available Residual feed intake (RFI is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs, candidate genes and biological pathways involved in regulating RFI using Genome-wide association (GWA and pathway analyses. A total of 596 Yorkshire boars with phenotypes for two different measures of RFI (RFI1 and 2 and 60k genotypic data was used. Genome-wide association analysis was performed using a univariate mixed model and 12 and 7 SNPs were found to be significantly associated with RFI1 and RFI2, respectively. Several genes such as XIRP2, TTC29, SOGA1, MAS1, GRK5, PROX1, GPR155 and ZFYVE26 were identified as putative candidates for RFI based on their genomic location in the vicinity of these SNPs. Genes located within 50 kilo base pairs of SNPs significantly associated with RFI and RFI2 (q-value ≤ 0.2 were subsequently used for pathway analyses. These analyses were performed by assigning genes to biological pathways and then testing the association of individual pathways with RFI using a Fisher’s exact test. Metabolic pathway was significantly associated with both RFIs. Other biological pathways regulating phagosome, tight junctions, olfactory transduction, and insulin secretion were significantly associated with both RFI traits when relaxed threshold for cut-off p-value was used (p ≤ 0.05. These results implied porcine RFI is regulated by multiple biological mechanisms, although the metabolic processes might be the most important. Olfactory transduction pathway controlling the perception of feed via smell, insulin pathway controlling food intake might be important pathways for RFI. Furthermore, our study revealed key genes and genetic variants that control feed efficiency that could potentially be useful for genetic selection of more feed efficient pigs.

  19. [Xenoestrogens: endocrine disrupting compounds].

    Science.gov (United States)

    Wozniak, Milena; Murias, Marek

    2008-11-01

    In recent years much attention has been paid to the issues of chemicals that disrupt the normal function of endocrine system, namely xenoestrogens. These chemicals can mimic the activity of endogenous estrogens, antagonize their interaction with estrogen receptors or disrupt the synthesis, metabolism and functions of endogenous female hormones. Due to the fact that they act thanks to many different mechanisms, it is very difficult to estimate their estrogenic activity by means of a simple tests. The important issue remains the fact that xenoestrogens may have a positive or negative influence on the function of the endocrine system. It seems to be very important that there are many sources of xenoestrogens, that is not only vegetables and fruit (phytoestrogens), but also metals (Co, Cu, Ni, Cr, Pb), dental appliances (alkilphenols), food containers or blood containers (PVC--polyvinyl chloride, DEHP--di-(2-ethylhexyl) phthalate), cosmetics (parabens) and pesticides (DDT--dichlor-diphenyl-trichlorethylane, endosulfane).

  20. Disrupted Refugee Family Life

    DEFF Research Database (Denmark)

    Shapiro, Ditte Krogh

    2017-01-01

    Fleeing civil war involves managing life threatening events and multiple disruptions of everyday life. The theoretical potentials of analysing the recreation of everyday family life among Syrian refugees in Denmark is explored based on conceptualizations that emphasize the collective agency...... war and struggle to recreate an everyday life in exile is to contribute with contextualization and expansion of mainstream understandings of family life, suffering, and resilience in refugee family trajectories in multiple contexts....

  1. Residual nilpotence and residual solubility of groups

    International Nuclear Information System (INIS)

    Mikhailov, R V

    2005-01-01

    The properties of the residual nilpotence and the residual solubility of groups are studied. The main objects under investigation are the class of residually nilpotent groups such that each central extension of these groups is also residually nilpotent and the class of residually soluble groups such that each Abelian extension of these groups is residually soluble. Various examples of groups not belonging to these classes are constructed by homological methods and methods of the theory of modules over group rings. Several applications of the theory under consideration are presented and problems concerning the residual nilpotence of one-relator groups are considered.

  2. Association between degradation of pharmaceuticals and endocrine-disrupting compounds and microbial communities along a treated wastewater effluent gradient in Lake Mead

    Science.gov (United States)

    Blunt, Susanna M.; Sackett, Joshua D.; Rosen, Michael R.; Benotti, Mark J.; Trenholm, Rebecca A.; Vanderford, Brett J.; Hedlund, Brian P.; Moser, Duane P.

    2018-01-01

    The role of microbial communities in the degradation of trace organic contaminants in the environment is little understood. In this study, the biotransformation potential of 27 pharmaceuticals and endocrine-disrupting compounds was examined in parallel with a characterization of the native microbial community in water samples from four sites variously impacted by urban run-off and wastewater discharge in Lake Mead, Nevada and Arizona, USA. Samples included relatively pristine Colorado River water at the upper end of the lake, nearly pure tertiary-treated municipal wastewater entering via the Las Vegas Wash, and waters of mixed influence (Las Vegas Bay and Boulder Basin), which represented a gradient of treated wastewater effluent impact. Microbial diversity analysis based on 16S rRNA gene censuses revealed the community at this site to be distinct from the less urban-impacted locations, although all sites were similar in overall diversity and richness. Similarly, Biolog EcoPlate assays demonstrated that the microbial community at Las Vegas Wash was the most metabolically versatile and active. Organic contaminants added as a mixture to laboratory microcosms were more rapidly and completely degraded in the most wastewater-impacted sites (Las Vegas Wash and Las Vegas Bay), with the majority exhibiting shorter half-lives than at the other sites or in a bacteriostatic control. Although the reasons for enhanced degradation capacity in the wastewater-impacted sites remain to be established, these data are consistent with the acclimatization of native microorganisms (either through changes in community structure or metabolic regulation) to effluent-derived trace contaminants. This study suggests that in urban, wastewater-impacted watersheds, prior exposure to organic contaminants fundamentally alters the structure and function of microbial communities, which in turn translates into greater potential for the natural attenuation of these compounds compared to more pristine

  3. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL.

    Science.gov (United States)

    Dawidowska, Małgorzata; Kosmalska, Maria; Sędek, Łukasz; Szczepankiewicz, Aleksandra; Twardoch, Magdalena; Sonsala, Alicja; Szarzyńska-Zawadzka, Bronisława; Derwich, Katarzyna; Lejman, Monika; Pawelec, Katarzyna; Obitko-Płudowska, Agnieszka; Pawińska-Wąsikowska, Katarzyna; Kwiecińska, Kinga; Kołtan, Andrzej; Dyla, Agnieszka; Grzeszczak, Władysław; Kowalczyk, Jerzy R; Szczepański, Tomasz; Ziętkiewicz, Ewa; Witt, Michał

    2016-07-18

    Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07-5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05-3.52, P = 0.03, MRD-day33 and MRD-week12, P RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28-12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61-28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL.

  4. Practical recommendations for the management of cardiovascular risk associated with atherogenic dyslipidemia, with special attention to residual risk. Spanish adaptation of a European Consensus of Experts.

    Science.gov (United States)

    This document has discussed clinical approaches to managing cardiovascular risk in clinical practice, with special focus on residual cardiovascular risk associated with lipid abnormalities, especially atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence and its impact on cardiovascular risk. AD can be defined by high fasting triglyceride levels (≥2.3mmol/L / ≥200mg/dL) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1,0 / 40 and ≤1,3mmol/L / 50mg/dL in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low density lipoprotein (LDL) lowering therapy with statins (±ezetimibe) are recommended by experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Others clinical condictions in which fenofibrate may be prescribed include patients with very high TGs (≥5.6mmol/L / 500mg/dL), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate-statin combination was considered by the experts to benefit from a favorable benefit-risk profile. In conclusion, cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  5. A comparison of equilibrium partitioning and critical body residue approaches for predicting toxicity of sediment-associated fluoranthene to freshwater amphipods

    Energy Technology Data Exchange (ETDEWEB)

    Driscoll, S.K. [Univ. of Michigan, Ann Arbor, MI (United States). Cooperative Inst. for Limnology and Ecosystem Research; Landrum, P.F. [National Oceanic and Atmospheric Administration, Ann Arbor, MI (United States). Great Lakes Environmental Research Lab.

    1997-10-01

    Equilibrium partitioning (EqP) theory predicts that the effects of organic compounds in sediments can be assessed by comparison of organic carbon-normalized sediment concentrations and estimated pore-water concentrations to effects determined in water-only exposures. A complementary approach, the critical body residue (CBR) theory, examines actual body burdens in relation to toxic effects. Critical body residue theory predicts that the narcotic effects of nonpolar compounds should be essentially constant for similar organisms, and narcosis should be observed at body burdens of 2 to 8 {micro}mol/g tissue. This study compares these two approaches for predicting toxicity of the polycyclic aromatic hydrocarbon (PAH) fluoranthene. The freshwater amphipods Hyalella azteca and Diporeia spp. were exposed for up to 30 d to sediment spiked with radiolabeled fluoranthene at concentrations of 0.1 (trace) to 3.940 nmol/g dry weight (= 346 {micro}mol/g organic carbon). Mean survival of Diporeia was generally high (>70%) and not significantly different from that of control animals. This result agrees with EqP predictions, because little mortality was observed for Diporeia in 10-d water-only exposures to fluoranthene in previous studies. After 10-d exposures, mortality of H. azteca was not significantly different from that of controls, even though measured interstitial water concentrations exceeded the previously determined 10-d water-only median lethal concentration (LC50). Equilibrium partitioning overpredicted fluoranthene sediment toxicity in this species. More mortality was observed for H. azteca at later time points, and a 16-d LC50 of 3.550 nmol/g dry weight sediment (291 {micro}mol/g organic carbon) was determined. A body burden of 1.10 {micro}mol fluoranthene-equivalents/g wet weight in H. azteca was associated with 50% mortality after 16-d exposures. Body burdens as high as 5.9 {micro}mol/g wet weight resulted in little mortality in Diporeia.

  6. The atherogenic dyslipidemia ratio [log(TG/HDL-C] is associated with residual vascular risk, beta-cell function loss and microangiopathy in type 2 diabetes females

    Directory of Open Access Journals (Sweden)

    Hermans Michel P

    2012-10-01

    Full Text Available Abstract Background Atherogenic dyslipidemia (AD, defined as low HDL-C plus elevated triglycerides (TG, comorbid to T2DM, increases cardiometabolic risk for CAD even when LDL-C is at target. In T2DM males, AD was shown to correlate with β-cell function loss, yet it is not established whether this applies across gender. Aim To establish the prevalence and severity of AD in T2DM females, and to determine how it relates to cardiometabolic phenotype, glucose homeostasis, micro- and macrovascular complications, and 10-year absolute CV risk (UKPDS Risk Engine. Methods 340 T2DM females were ranked according to quintiles (Q of the continuous variable log(TG/HDL-C, with AD prevalence defined as HDL-C -1 plus TG ≥150 mg.dL-1, and β-cell function assessed with HOMA. Results AD prevalence was 35%; mean HDL-C and TG were 52 (15 and 160 (105 mg.dL-1. AD was significantly related to central fat, metabolic syndrome, sedentarity and skeletal sarcopenia, as well as to hsCRP, fibrinogen, uric acid, cystatin-C, Big ET-1, and 10-year UKPDS CV risk. AD correlated stepwise with lower β-cell function and hyperbolic product, and with accelerated loss of residual insulin secretion, higher HbA1c and prevalent microangiopathy. Conclusions log(TG/HDL-C is a simple means to grade AD and residual macrovascular risk in T2DM females. This ratio associates with major non-LDL cardiometabolic variables and ranks predicted CAD risk. In addition, log(TG/HDL-C identifies worsening glucose homeostasis, poorer glycemic control, and prevalent microangiopathy.

  7. Disruption - Access cards service

    CERN Multimedia

    2014-01-01

    We would like to inform you that between 10 November and 15 December 2014, the access cards service in Building 55 will be disrupted, as the GS Department has decided to improve the facilities for users of this building. During the work, you will find the registration, biometric registration and dosimeter exchange services on the second floor of Building 55 and the vehicle sticker service on the ground floor along with the access cards service. We thank you for your understanding and apologise for any inconvenience caused.

  8. Engineering aspects of disruption current decay

    International Nuclear Information System (INIS)

    Murray, J.G.

    1983-11-01

    Engineering features associated with the configuration of a tokamak can affect the amount of energy that produces melting and damage to the limiters or internal wall surfaces as the result of a major disruption. During the current decay period of a major thermal disruption, the energy that can damage a wall or limiter comes from the external magnetic field. By providing a good conducting torus near the plasma and increasing the plasma circuit resistance, this magnetic energy (transferred by way of the plasma circuit) can be minimized. This report addresses engineering design features to reduce the energy deposited on the inner torus surface that produces melting of the structures

  9. Relativistic tidal disruption events

    Directory of Open Access Journals (Sweden)

    Levan A.

    2012-12-01

    Full Text Available In March 2011 Swift detected an extremely luminous and long-lived outburst from the nucleus of an otherwise quiescent, low luminosity (LMC-like galaxy. Named Swift J1644+57, its combination of high-energy luminosity (1048 ergs s−1 at peak, rapid X-ray variability (factors of >100 on timescales of 100 seconds and luminous, rising radio emission suggested that we were witnessing the birth of a moderately relativistic jet (Γ ∼ 2 − 5, created when a star is tidally disrupted by the supermassive black hole in the centre of the galaxy. A second event, Swift J2058+0516, detected two months later, with broadly similar properties lends further weight to this interpretation. Taken together this suggests that a fraction of tidal disruption events do indeed create relativistic outflows, demonstrates their detectability, and also implies that low mass galaxies can host massive black holes. Here, I briefly outline the observational properties of these relativistic tidal flares observed last year, and their evolution over the first year since their discovery.

  10. Engineered Surfaces for Mitigation of Insect Residue Adhesion

    Science.gov (United States)

    Siochi, Emilie J.; Smith, Joseph G.; Wohl, Christopher J.; Gardner, J. M.; Penner, Ronald K.; Connell, John W.

    2013-01-01

    Maintenance of laminar flow under operational flight conditions is being investigated under NASA s Environmentally Responsible Aviation (ERA) Program. Among the challenges with natural laminar flow is the accretion of residues from insect impacts incurred during takeoff or landing. Depending on air speed, temperature, and wing structure, the critical residue height for laminar flow disruption can be as low as 4 microns near the leading edge. In this study, engineered surfaces designed to minimize insect residue adhesion were examined. The coatings studied included chemical compositions containing functional groups typically associated with abhesive (non-stick) surfaces. To reduce surface contact by liquids and enhance abhesion, the engineered surfaces consisted of these coatings doped with particulate additives to generate random surface topography, as well as coatings applied to laser ablated surfaces having precision patterned topographies. Performance evaluation of these surfaces included contact angle goniometry of pristine coatings and profilometry of surfaces after insect impacts were incurred in laboratory scale tests, wind tunnel tests and flight tests. The results illustrate the complexity of designing antifouling surfaces for effective insect contamination mitigation under dynamic conditions and suggest that superhydrophobic surfaces may not be the most effective solution for preventing insect contamination on aircraft wing leading edges.

  11. Cell disruption for microalgae biorefineries.

    Science.gov (United States)

    Günerken, E; D'Hondt, E; Eppink, M H M; Garcia-Gonzalez, L; Elst, K; Wijffels, R H

    2015-01-01

    Microalgae are a potential source for various valuable chemicals for commercial applications ranging from nutraceuticals to fuels. Objective in a biorefinery is to utilize biomass ingredients efficiently similarly to petroleum refineries in which oil is fractionated in fuels and a variety of products with higher value. Downstream processes in microalgae biorefineries consist of different steps whereof cell disruption is the most crucial part. To maintain the functionality of algae biochemicals during cell disruption while obtaining high disruption yields is an important challenge. Despite this need, studies on mild disruption of microalgae cells are limited. This review article focuses on the evaluation of conventional and emerging cell disruption technologies, and a comparison thereof with respect to their potential for the future microalgae biorefineries. The discussed techniques are bead milling, high pressure homogenization, high speed homogenization, ultrasonication, microwave treatment, pulsed electric field treatment, non-mechanical cell disruption and some emerging technologies. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1.

    Science.gov (United States)

    Benzeno, S; Lu, F; Guo, M; Barbash, O; Zhang, F; Herman, J G; Klein, P S; Rustgi, A; Diehl, J A

    2006-10-12

    Although cyclin D1 is overexpressed in a significant number of human cancers, overexpression alone is insufficient to promote tumorigenesis. In vitro studies have revealed that inhibition of cyclin D1 nuclear export unmasks its neoplastic potential. Cyclin D1 nuclear export depends upon phosphorylation of a C-terminal residue, threonine 286, (Thr-286) which in turn promotes association with the nuclear exportin, CRM1. Mutation of Thr-286 to a non-phosphorylatable residue results in a constitutively nuclear cyclin D1 protein with significantly increased oncogenic potential. To determine whether cyclin D1 is subject to mutations that inhibit its nuclear export in human cancer, we have sequenced exon 5 of cyclin D1 in primary esophageal carcinoma samples and in cell lines derived from esophageal cancer. Our work reveals that cyclin D1 is subject to mutations in primary human cancer. The mutations identified specifically disrupt phosphorylation of cyclin D1 at Thr-286, thereby enforcing nuclear accumulation of cyclin D1. Through characterization of these mutants, we also define an acidic residue within the C-terminus of cyclin D1 that is necessary for recognition and phosphorylation of cyclin D1 by glycogen synthase kinase-3 beta. Finally, through construction of compound mutants, we demonstrate that cell transformation by the cancer-derived cyclin D1 alleles correlates with their ability to associate with and activate CDK4. Our data reveal that cyclin D1 is subject to mutations in primary human cancer that specifically disrupt phosphorylation-dependent nuclear export of cyclin D1 and suggest that such mutations contribute to the genesis and progression of neoplastic growth.

  13. Basis for Selection of a Residual Waste Retrieval System for Gunite and Associated Tank W-9 at the Oak Ridge National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, B.E

    2000-10-23

    Waste retrieval and transfer operations at the Gunite{trademark} and Associated Tanks (GAATs) Remediation Project have been successfully accomplished using the Tank Waste Retrieval System. This system is composed of the Modified Light-Duty Utility Arm, Houdini Vehicle, Waste Dislodging and Conveyance System, Hose Management Arm, and Sludge Conditioning System. GAAT W-9 has been used as a waste-consolidation and batch-transfer tank during the retrieval of sludges and supernatants from the seven Gunite tanks in the North and South tank farms at Oak Ridge National Laboratory. Tank W-9 was used as a staging tank for the transfers to the Melton Valley Storage Tanks (MVSTs). A total of 18 waste transfers from W-9 occurred between May 25, 1999, and March 30, 2000. Most of these transfers were accomplished using the PulsAir Mixer to mobilize and mix the slurry and a submersible retrieval-transfer pump to transfer the slurry through the Sludge Conditioning System and the {approx}1-mile long, 2-in.-diam waste-transfer line to the MVSTs. The transfers from W-9 have consisted of low-solids-content slurries with solids contents ranging from {approx}2.8 to 6.8 mg/L. Of the initial {approx}88,000 gal of wet sludge estimated in the GAATs, a total of {approx}60,451 gal have been transferred to the MVSTs via tank W-9 as of March 30, 2000. Once the waste-consolidation operations and transfers from W-9 to the MVSTs are completed, the remaining material in W-9 will be mobilized and transferred to the active waste system, Bethel Valley Evaporator Service Tank W-23. Tank W-23 will serve as a batch tank for the final waste transfers from tank W-9 to the MVSTs. This report provides a summary of the requirements and recommendations for the final waste retrieval system for tank W-9, a compilation of the sample analysis data for the sludge in W-9, and brief descriptions of the various waste-retrieval system concepts that were considered for this task. The recommended residual waste retrieval

  14. Endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Mandrup, Karen

    BACKGROUND: Endocrine disrupting chemicals (EDCs) may contribute to reproductive changes in boys in the Western world, however, less is known about influence of EDCs in women. The incidence of precocious breast development is increasing in USA and Europe and mammary gland development has been...... gland development before puberty in whole mounted mammary glands and in adults in histological sections of the mammary glands. Moreover, female offspring were evaluated for external genital malformations. The EDCs studied for mammary gland effects were the estrogenic compounds ethinyl estradiol...... were sensitive to EDCs. EDCs with estrogenic mode of action appeared to increase mammary outgrowth in prepubertal female rats and a potent model compound, ethinyl estradiol, increased the density in females and males and the number of terminal end buds in male rats. Histological examination showed...

  15. Overview of core disruptive accidents

    International Nuclear Information System (INIS)

    Marchaterre, J.F.

    1977-01-01

    An overview of the analysis of core-disruptive accidents is given. These analyses are for the purpose of understanding and predicting fast reactor behavior in severe low probability accident conditions, to establish the consequences of such conditions and to provide a basis for evaluating consequence limiting design features. The methods are used to analyze core-disruptive accidents from initiating event to complete core disruption, the effects of the accident on reactor structures and the resulting radiological consequences are described

  16. Increased neurovirulence and reactivation of the herpes simplex virus type 1 latency associated transcript (LAT) negative mutant dLAT2903 with a disrupted LAT miR-H2

    Science.gov (United States)

    Jiang, Xianzhi; Brown, Don; Osorio, Nelson; Hsiang, Chinhui; BenMohamed, Lbachir; Wechsler, Steven L.

    2015-01-01

    At least six microRNAs (miRNAs) appear to be encoded by the latency associated transcript (LAT) of herpes simplex virus type 1 (HSV-1). The gene for ICP0, an important immediate early (IE) viral protein, is antisense to, and overlaps with, the region of LAT from which miRNA H2 (miR-H2) is derived. We recently reported that a mutant (McK-ΔH2) disrupted for miR-H2 on the wild type HSV-1 strain McKrae genomic background has increased ICP0 expression, increased neurovirulence, and slightly more rapid reactivation. We report here that HSV-1 mutants deleted for the LAT promoter nonetheless make significant amounts of miR-H2 during lytic tissue culture infection, presumably via readthrough transcription from an upstream promoter. To determine if miR-H2 might also play a role in the HSV-1 latency-reactivation cycle of a LAT negative mutant, we constructed dLAT-ΔH2, in which miR-H2 is disrupted in dLAT2903 without altering the predicted amino acid sequence of the overlapping ICP0 open reading frame. Similar to McK-ΔH2, dLAT-ΔH2 expressed more ICP0, was more neurovirulent, and had increased reactivation in the mouse TG explant induced reactivation model of HSV-1 compared to its parental virus. Interestingly, although the increased reactivation of McK-ΔH2 compared to its parental wt virus was subtle and only detected at very early times after explant TG induced reactivation, the increased reactivation of dLAT-ΔH2 compared to its dLAT2903 parental virus appeared more robust and was significantly increased even at late times after induction. These results confirm that miR-H2 plays a role in modulating the HSV-1 reactivation phenotype. PMID:26069184

  17. Genome-wide association and systems genetic analyses of residual feed intake, daily feed consumption, backfat and weight gain in pigs

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Ostersen, Tage; Strathe, Anders Bjerring

    2014-01-01

    Feed efficiency is one of the major components determining costs of animal production. Residual feed intake (RFI) is defined as the difference between the observed and the expected feed intake given a certain production. Residual feed intake 1 (RFI1) was calculated based on regression of individual...... daily feed intake (DFI) on initial test weight and average daily gain. Residual feed intake 2 (RFI2) was as RFI1 except it was also regressed with respect to backfat (BF). It has been shown to be a sensitive and accurate measure for feed efficiency in livestock but knowledge of the genomic regions...

  18. Current concepts in neuroendocrine disruption.

    Science.gov (United States)

    León-Olea, Martha; Martyniuk, Christopher J; Orlando, Edward F; Ottinger, Mary Ann; Rosenfeld, Cheryl; Wolstenholme, Jennifer; Trudeau, Vance L

    2014-07-01

    feeding in fish. There is growing evidence for the association between environmental contaminant exposures and diseases with strong neuroendocrine components, for example decreased fecundity, neurodegeneration, and cardiac disease. It is critical to consider the timing of exposures of neuroendocrine disruptors because embryonic stages of central nervous system development are exquisitely sensitive to adverse effects. There is also evidence for epigenetic and transgenerational neuroendocrine disrupting effects of some pollutants. We must now consider the impacts of neuroendocrine disruptors on reproduction, development, growth and behaviors, and the population consequences for evolutionary change in an increasingly contaminated world. This review examines the evidence to date that various so-called neuroendocrine disruptors can induce such effects often at environmentally-relevant concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Current Concepts in Neuroendocrine Disruption

    Science.gov (United States)

    2014-01-01

    feeding in fish. There is growing evidence for the association between environmental contaminant exposures and diseases with strong neuroendocrine components, for example decreased fecundity, neurodegeneration, and cardiac disease. It is critical to consider the timing of exposures of neuroendocrine disruptors because embryonic stages of central nervous system development are exquisitely sensitive to adverse effects. There is also evidence for epigenetic and transgenerational neuroendocrine disrupting effects of some pollutants. We must now consider the impacts of neuroendocrine disruptors on reproduction, development, growth and behaviors, and the population consequences for evolutionary change in an increasingly contaminated world. This review examines the evidence to date that various so-called neuroendocrine disruptors can induce such effects often at environmentally-relevant concentrations. PMID:24530523

  20. MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith-Magenis and fragile X syndromes.

    Science.gov (United States)

    Mullegama, Sureni V; Pugliesi, Loren; Burns, Brooke; Shah, Zalak; Tahir, Raiha; Gu, Yanghong; Nelson, David L; Elsea, Sarah H

    2015-06-01

    Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith-Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders.

  1. Disrupted white matter integrity is associated with cognitive deficits in patients with amnestic mild cognitive impairment: An atlas-based study

    Directory of Open Access Journals (Sweden)

    Duan Liu

    2016-06-01

    Full Text Available Objective: This study investigated white matter integrity in patients with amnestic mild cognitive impairment by diffusion tensor imaging. Methods: A total of 83 patients with amnestic mild cognitive impairment and 85 elderly healthy controls underwent neuropsychological testing and a diffusion tensor imaging scan. Whole-brain white matter data were parcellated into 50 regions based on the anatomical ICBM-DTI-81 atlas, and regional diffusion metrics consisting of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated for each region. Diffusion tensor imaging indices were compared between groups, and it was determined that between-group differences were significantly correlated with neurocognitive performance. Results: Relative to the healthy controls group, the amnestic mild cognitive impairment group exhibited poorer cognitive performance in all neuropsychological tests except the complex figure test (p = 0.083 and showed decreased mean fractional anisotropy in the fornix, increased mean diffusivity in the fornix and bilateral uncinate fasciculus, elevated axial diffusivity in the fornix and genu of corpus callosum, and elevated radial diffusivity in the fornix and bilateral uncinate fasciculus (p < 0.05. Behaviorally, integrity of the bilateral uncinate fasciculus was correlated positively with episodic memory function, while left uncinate fasciculus integrity was positively associated with language function in the amnestic mild cognitive impairment group (p < 0.05. Conclusion: White matter abnormalities in neural pathways associated with memory were correlated with neurocognitive deficiencies in amnestic mild cognitive impairment. Given that amnestic mild cognitive impairment is putatively a prodromal syndrome for Alzheimer’s disease, this study furthers our understanding of the white matter changes associated with Alzheimer’s disease pathogenesis in the predementia stage.

  2. Association between a disrupted-in-schizophrenia 1 (DISC1) single nucleotide polymorphism and schizophrenia in a combined Scandinavian case-control sample

    DEFF Research Database (Denmark)

    Saetre, Peter; Agartz, Ingrid; De Franciscis, Alessandra

    2008-01-01

    after correction for multiple testing. However, the minor allele of rs3737597 (frequency 2%) in the 3'-untranslated region (UTR), previously identified as a risk allele in Finnish families, was significantly and consistently associated with the disorder across the three samples, (p-value corrected...... for multiple testing was 0.002). Our results suggest that a relatively uncommon DISC1 mutation, which increases the susceptibility for schizophrenia may be segregating in the Scandinavian population, and support the view that common DISC1 SNP alleles are unlikely to account for a substantial proportion...

  3. Short- and long-term health consequences of sleep disruption.

    Science.gov (United States)

    Medic, Goran; Wille, Micheline; Hemels, Michiel Eh

    2017-01-01

    Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care

  4. Disruption of zebrafish cyclin G-associated kinase (GAK function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development

    Directory of Open Access Journals (Sweden)

    Szeto Daniel P

    2010-01-01

    Full Text Available Abstract Background The J-domain-containing protein auxilin, a critical regulator in clathrin-mediated transport, has been implicated in Drosophila Notch signaling. To ask if this role of auxilin is conserved and whether auxilin has additional roles in development, we have investigated the functions of auxilin orthologs in zebrafish. Results Like mammals, zebrafish has two distinct auxilin-like molecules, auxilin and cyclin G-associated kinase (GAK, differing in their domain structures and expression patterns. Both zebrafish auxilin and GAK can functionally substitute for the Drosophila auxilin, suggesting that they have overlapping molecular functions. Still, they are not completely redundant, as morpholino-mediated knockdown of the ubiquitously expressed GAK alone can increase the specification of neuronal cells, a known Notch-dependent process, and decrease the expression of Her4, a Notch target gene. Furthermore, inhibition of GAK function caused an elevated level of apoptosis in neural tissues, resulting in severe degeneration of neural structures. Conclusion In support of the notion that endocytosis plays important roles in Notch signaling, inhibition of zebrafish GAK function affects embryonic neuronal cell specification and Her4 expression. In addition, our analysis suggests that zebrafish GAK has at least two functions during the development of neural tissues: an early Notch-dependent role in neuronal patterning and a late role in maintaining the survival of neural cells.

  5. Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation.

    Science.gov (United States)

    Shang, Jian; Li, Lixia; Wang, Xiaobing; Pan, Huaqin; Liu, Shi; He, Ruohang; Li, Jin; Zhao, Qiu

    2016-01-01

    Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5's influence on inflammatory bowel diseases (IBDs), we investigated TRAF5 deficiency's effect on dextran sulfate sodium- (DSS-) induced colitis. Colitis was induced in TRAF5 knockout (KO) mice and their wild-type (WT) littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4(+) T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4(+) T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.

  6. Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation

    Directory of Open Access Journals (Sweden)

    Jian Shang

    2016-01-01

    Full Text Available Tumor necrosis factor (TNF receptor-associated factor 5 (TRAF5 is a key mediator of TNF receptor superfamily members and is important in both T helper (Th cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5’s influence on inflammatory bowel diseases (IBDs, we investigated TRAF5 deficiency’s effect on dextran sulfate sodium- (DSS- induced colitis. Colitis was induced in TRAF5 knockout (KO mice and their wild-type (WT littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4+ T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4+ T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.

  7. Targeting of Slc25a21 Is Associated with Orofacial Defects and Otitis Media Due to Disrupted Expression of a Neighbouring Gene

    Science.gov (United States)

    Maguire, Simon; Estabel, Jeanne; Ingham, Neil; Pearson, Selina; Ryder, Edward; Carragher, Damian M.; Walker, Nicolas; Bussell, James; Chan, Wai-In; Keane, Thomas M.; Adams, David J.; Scudamore, Cheryl L.; Lelliott, Christopher J.; Ramírez-Solis, Ramiro; Karp, Natasha A.; Steel, Karen P.; White, Jacqueline K.; Gerdin, Anna-Karin

    2014-01-01

    Homozygosity for Slc25a21tm1a(KOMP)Wtsi results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21tm1a(KOMP)Wtsi despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21tm1b(KOMP)Wtsi and Slc25a21tm1d(KOMP)Wtsi alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3′ of the target gene, was reduced in homozygous Slc25a21tm1a(KOMP)Wtsi mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21tm1a(KOMP)Wtsi mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms. PMID:24642684

  8. Disrupted lymph node and splenic stroma in mice with induced inflammatory melanomas is associated with impaired recruitment of T and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Saïdi M Soudja

    Full Text Available Migration of dendritic cells (DC from the tumor environment to the T cell cortex in tumor-draining lymph nodes (TDLN is essential for priming naïve T lymphocytes (TL to tumor antigen (Ag. We used a mouse model of induced melanoma in which similar oncogenic events generate two phenotypically distinct melanomas to study the influence of tumor-associated inflammation on secondary lymphoid organ (SLO organization. One tumor promotes inflammatory cytokines, leading to mobilization of immature myeloid cells (iMC to the tumor and SLO; the other does not. We report that inflammatory tumors induced alterations of the stromal cell network of SLO, profoundly altering the distribution of TL and the capacity of skin-derived DC and TL to migrate or home to TDLN. These defects, which did not require tumor invasion, correlated with loss of fibroblastic reticular cells in T cell zones and in impaired production of CCL21. Infiltrating iMC accumulated in the TDLN medulla and the splenic red pulp. We propose that impaired function of the stromal cell network during chronic inflammation induced by some tumors renders spleens non-receptive to TL and TDLN non-receptive to TL and migratory DC, while the entry of iMC into these perturbed SLO is enhanced. This could constitute a mechanism by which inflammatory tumors escape immune control. If our results apply to inflammatory tumors in general, the demonstration that SLO are poorly receptive to CCR7-dependent migration of skin-derived DC and naïve TL may constitute an obstacle for proposed vaccination or adoptive TL therapies of their hosts.

  9. Female-to-male sex reversal associated with unique Xp21.2 deletion disrupting genomic regulatory architecture of the dosage-sensitive sex reversal region.

    Science.gov (United States)

    Dangle, Pankaj; Touzon, María Sol; Reyes-Múgica, Miguel; Witchel, Selma F; Rajkovic, Aleksandar; Schneck, Francis X; Yatsenko, Svetlana A

    2017-10-01

    The XX male disorder of sex development (DSD) is a rare condition that is most commonly associated with the presence of the SRY gene on one of the X chromosomes due to unequal crossing-over between sex chromosomes during spermatogenesis. However, in about 20% of the XX male individuals, SRY is missing, although these persons have at least some testis differentiation. The genetic basis of genital ambiguity and the mechanisms triggering testis development in such patients remain unknown. The proband with 46,XX SRY -negative testicular DSD was screened for point mutations by whole exome sequencing and CNVs using a high-resolution DSD gene-targeted and whole genome array comparative genomic hybridisation. The identified Xp21.2 genomic alteration was further characterised by direct sequencing of the breakpoint junctions and bioinformatics analysis. A unique, 80 kb microdeletion removing the regulatory sequences and the NR0B1 gene was detected by microarray analysis. This deletion disturbs the human-specific genomic architecture of the Xp21.2 dosage-sensitive sex (DSS) reversal region in the XX patient with male-appearing ambiguous genitalia and ovotestis. Duplication of the DSS region containing the MAGEB and NR0B1 genes has been implicated in testis repression and sex reversal. Identification of this microdeletion highlights the importance of genomic integrity in the regulation and interaction of sex determining genes during gonadal development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Targeting of Slc25a21 is associated with orofacial defects and otitis media due to disrupted expression of a neighbouring gene.

    Directory of Open Access Journals (Sweden)

    Simon Maguire

    Full Text Available Homozygosity for Slc25a21(tm1a(KOMPWtsi results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21(tm1a(KOMPWtsi despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21(tm1b(KOMPWtsi and Slc25a21(tm1d(KOMPWtsi alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3' of the target gene, was reduced in homozygous Slc25a21(tm1a(KOMPWtsi mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21(tm1a(KOMPWtsi mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms.

  11. Social network disruption as a major factor associated with psychological distress 3 years after the 2004 Niigata-Chuetsu earthquake in Japan.

    Science.gov (United States)

    Oyama, Mari; Nakamura, Kazutoshi; Suda, Yuko; Someya, Toshiyuki

    2012-03-01

    The 2004 Niigata-Chuetsu earthquake of Japan caused a great deal of damage, and people living in the affected region are still struggling to reconstruct their lives. The aim of this study was to determine factors associated with psychological distress in people living in a town at the epicenter 3 years after the earthquake. We conducted a cross-sectional study from June 2007 to January 2008. Participants included 225 individuals living in Kawaguchi (age ≥20 years) who reported psychological symptoms. Information on family structure, employment status, alcohol use, social network, and extent of house damage was elicited by public health nurses conducting structured interviews. Levels of psychological distress were assessed with the Kessler Psychological Distress Scale (K10), with a K10 score ≥25 defined as psychological distress. The mean age of participants was 66.1 ± 12.9 years. The prevalence of psychological distress varied among different employment classes, being 5/73 (6.8%) for participants with paid employment, 12/50 (24.0%) for full-time housewives, and 11/101 (10.9%) for those who were unemployed (χ(2) = 8.42, P = 0.015). It also varied between participants who had lost contact with people in the community and those who had no change in social contact [9/20 (45.0%) vs. 19/189 (10.1%), respectively; χ(2) = 19.04, P earthquake psychological distress and require appropriate care.

  12. Heavy metal water pollution associated with the use of sewage sludge compost and limestone outcrop residue for soil restoration: effect of saline irrigation.

    Science.gov (United States)

    Pérez-Gimeno, Ana; Navarro-Pedreño, Jose; Gómez, Ignacio; Belén Almedro-Candel, María; Jordán, Manuel M.; Bech, Jaume

    2015-04-01

    The use of composted sewage sludge and limestone outcrop residue in soil restoration and technosol making can influence the mobility of heavy metals into groundwater. The use of compost from organic residues is a common practice in soil and land rehabilitation, technosol making, and quarry restoration (Jordán et al. 2008). Compost amendments may improve the physical, chemical, and biological properties of soils (Jordão et al. 2006; Iovieno et al. 2009). However, the use of compost and biosolids may have some negative effects on the environment (Karaca 2004; Navarro-Pedreño et al. 2004). This experiment analyzed the water pollution under an experimental design based on the use of columns (0-30 cm) formed by both wastes. Two waters of different quality (saline and non-saline) were used for irrigation. The presence of heavy metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) in the leachates was checked under controlled conditions inside a greenhouse (mean values: 20°±5°C and around 60% relative humidity). Sixteen 30-cm tall columns made of PVC pipe with internal diameters of 10.5 cm were prepared. The columns were filled with one of these materials: either sewage sludge compost (SW) or limestone outcrop residue (LR), fraction (<4 mm). The columns were irrigated with 2000 mL/week (230 mm) for twelve weeks (April to July). Half of them were irrigated with non-saline water (NS) and the others were so with saline water (S) from the beginning of the experiment. Four treatments combining the quality of the irrigation water (saline and non-saline) and wastes were studied: SW-NS, SW-S, LR-NS, and LR-S. After 24 hours of irrigation on the first day of each week, the leachates were taken and analyzed the heavy metal content (AAS-ES espectometer). The environmental risk due to the presence of heavy metals associated with the use of these materials was very low in general (under 0.1 mg/L). The use of sewage sludge favoured the presence of these metals in the lecheates and no effect

  13. AIDS and economic disruption.

    Science.gov (United States)

    Johnson, G S

    1996-10-01

    Child and adult mortality increases in Cameroon due to AIDS will cause life expectancy to fall by as many as 8 years, from just over 50 to just over 40 years. The social consequences of AIDS include grieving, stigmatizing, and the large-scale disruption of family and community structures. Widows and widowers due to AIDS mortality are affected differently from each other, with the widows of men who have died from AIDS facing potential sociocultural and economic hardship. The economic consequences of AIDS in Bamenda and elsewhere in Cameroon will occur mainly through the epidemic's impact upon the size and quality of the labor force. By killing a significant number of male and female workers aged 15-60 years, AIDS will reduce the size and growth rate of the labor force. Despite, rapid population growth, labor is a relatively scarce factor of agricultural production in Cameroon. The spread of HIV in rural areas, combined with the intensity and scarcity of agricultural labor, suggests that AIDS will have an impact upon production and per capita incomes, and increase the already high rates of hunger and absolute poverty. In the context of HIV/AIDS, young people must be empowered to make informed decisions about sex. Adolescents are most at risk because they tend to experiment more than married couples and have many sex partners. Sexual activity begins as early as age 8 years and penetrative sex at age 13 or earlier. The author considers the factors which encourage adolescents to engage in sexual activities.

  14. Disrupting Ethnography through Rhizoanalysis

    Directory of Open Access Journals (Sweden)

    Diana Masny

    2014-10-01

    Full Text Available This article interrogates principles of ethnography in education proposed by Mills and Morton: raw tellings, analytic pattern, vignette and empathy. This article adopts a position that is uncomfortable, unconventional and interesting. It involves a deterritorialization/ rupture of ethnography in education in order to reterritorialize a different concept: rhizoanalysis, a way to position theory and data that is multilayered, complex and messy. Rhizoanalysis, the main focus of this article is not a method. It is an approach to research conditioned by a reality in which Deleuze and Guattari disrupt representation, interpretation and subjectivity. In this article, Multiple Literacies Theory, a theoretical and practical framework, becomes a lens to examine a rhizomatic study of a Korean family recently arrived to Australia and attending English as a second language classes. Observations and interviews recorded the daily lives of the family. The vignettes were selected by reading data intensively and immanently through a process of palpation, an innovative approach to educational research. Rhizoanalysis proposes to abandon the given and invent different ways of thinking about and doing research and what might happen when reading data differently, intensively and immanently, through Multiple Literacies Theory. Rhizoanalysis, a game-changer in the way research can be conducted, affords a different lens to tackle issues in education through research.

  15. Reproduction Symposium: does grazing on biosolids-treated pasture pose a pathophysiological risk associated with increased exposure to endocrine disrupting compounds?

    Science.gov (United States)

    Evans, N P; Bellingham, M; Sharpe, R M; Cotinot, C; Rhind, S M; Kyle, C; Erhard, H; Hombach-Klonisch, S; Lind, P M; Fowler, P A

    2014-08-01

    Biosolids (processed human sewage sludge), which contain low individual concentrations of an array of contaminants including heavy metals and organic pollutants such as polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB), and polychlorinated dibenzodioxins/polychlorinated dibenzofurans known to cause physiological disturbances, are increasingly being used as an agricultural fertilizer. This could pose a health threat to both humans and domestic and wild animal species. This review summarizes results of a unique model, used to determine the effects of exposure to mixtures of environmentally relevant concentrations of pollutants, in sheep grazed on biosolids-treated pastures. Pasture treatment results in nonsignificant increases in environmental chemical (EC) concentrations in soil. Whereas EC concentrations were increased in some tissues of both ewes and their fetuses, concentrations were low and variable and deemed to pose little risk to consumer health. Investigation of the effects of gestational EC exposure on fetal development has highlighted a number of issues. The results indicate that gestational EC exposure can adversely affect gonadal development (males and females) and that these effects can impact testicular morphology, ovarian follicle numbers and health, and the transcriptome and proteome in adult animals. In addition, EC exposure can be associated with altered expression of GnRH, GnRH receptors, galanin receptors, and kisspeptin mRNA within the hypothalamus and pituitary gland, gonadotroph populations within the pituitary gland, and regional aberrations in thyroid morphology. In most cases, these anatomical and functional differences do not result in altered peripheral hormone concentrations or reproductive function (e.g., lambing rate), indicating physiological compensation under the conditions tested. Physiological compensation is also suggested from studies that indicate that EC effects may be greater when exposure occurs either

  16. Disruption of metal ion homeostasis in soils is associated with nitrogen deposition-induced species loss in an Inner Mongolia steppe

    Science.gov (United States)

    Tian, Q.-Y.; Liu, N.-N.; Bai, W.-M.; Li, L.-H.; Zhang, W.-H.

    2015-06-01

    Enhanced deposition of atmospheric nitrogen (N) resulting from anthropogenic activities has negative impacts on plant diversity in ecosystems. Several mechanisms have been proposed to explain the species loss. Ion toxicity due to N deposition-induced soil acidification has been suggested to be responsible for species loss in acidic grasslands, while few studies have evaluated the role of soil-mediated homeostasis of ions in species loss under elevated N deposition in grasslands with neutral or alkaline soils. To determine whether soil-mediated processes are involved in changes in biodiversity induced by N deposition, the effects of 9-year N addition on soil properties, aboveground biomass (AGB) and species richness were investigated in an Inner Mongolia steppe. Low to moderate N addition rate (2, 4, 8 g N m-2 yr-1) significantly enhanced AGB of graminoids, while high N addition rate (≥ 16 g N m-2 yr-1) reduced AGB of forbs, leading to an overall increase in AGB of the community under low to moderate N addition rates. Forb richness was significantly reduced by N addition at rates greater than 8 g N m-2 yr-1, while no effect of N addition on graminoid richness was observed, resulting in decline in total species richness. N addition reduced soil pH, depleted base cations (Ca2+, Mg2+ and K+) and mobilized Mn2+, Fe3+, Cu2+ and Al3+ ions in soils. Soil inorganic-N concentration was negatively correlated with forb richness and biomass, explaining 23.59% variation of forb biomass. The concentrations of base cations (Ca2+ and Mg2+) and metal ions (Mn2+, Cu2+ and, Fe3+) showed positively and negatively linear correlation with forb richness, respectively. Changes in the metal ion concentrations accounted for 42.77% variation of forb richness, while reduction of base cations was not associated with the reduction in forb richness. These results reveal that patterns of plant biodiversity in the temperate steppe of Inner Mongolia are primarily driven by increases in metal ion

  17. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

    Science.gov (United States)

    Sheikh, Ishfaq A; Turki, Rola F; Abuzenadah, Adel M; Damanhouri, Ghazi A; Beg, Mohd A

    2016-01-01

    Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15-31 amino acid residues of SHBG and a commonality of 55-95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.

  18. Detection of Residual Levels and Associated Health Risk of Seven Pesticides in Fresh Eggplant and Tomato Samples from Narayanganj District, Bangladesh

    Directory of Open Access Journals (Sweden)

    Md. Nur Alam

    2015-01-01

    Full Text Available Residual levels of seven frequently used pesticides were investigated in 140 samples of two common vegetables, eggplants and tomatoes, from agricultural fields in the Narayanganj district of Bangladesh. The analysis of pesticide residues was performed by high-performance liquid chromatography with photodiode array detection. A large percentage of the eggplants (50% and tomatoes (60% from the Narayanganj district were contaminated with pesticides, and all of the levels were above the maximum residual limit (MRL proposed by the EC regulation. Diazinon was the most common (35% pesticide detected in the vegetable samples at a concentration of 45–450 times higher than the MRL. The health risk index for diazinon was highest for both eggplant and tomato samples, which may be due to its physiochemical properties. Fenitrothion and linuron are the two second most common types of pesticides detected in the vegetable samples. Regular monitoring of the use of common pesticides on vegetables should be conducted.

  19. Thigmotaxis Mediates Trail Odour Disruption.

    Science.gov (United States)

    Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

    2017-05-10

    Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

  20. Sleep disruption in chronic rhinosinusitis.

    Science.gov (United States)

    Mahdavinia, Mahboobeh; Schleimer, Robert P; Keshavarzian, Ali

    2017-05-01

    Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression. Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS. Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.

  1. Increased Placental Glucose Transport Rates in Pregnant Mice Carrying Fetuses with Targeted Disruption of Their Placental-Specific Igf2 Transcripts Are Not Associated with Raised Circulating Glucose Concentrations

    Directory of Open Access Journals (Sweden)

    Clive J. Petry

    2011-01-01

    Full Text Available At the beginning of the third week of pregnancy, mouse fetuses with targeted disruption of their paternally-transmitted insulin-like growth factor 2 gene placental-specific transcripts have growth-restricted placentas but normal body weights due to upregulated placental nutrient transport. We assessed whether increased placental glucose transport rates were associated with raised maternal glucose concentrations by performing intraperitoneal glucose tolerance tests (ipGTT in pregnant mice carrying knockout pups and comparing them with mice carrying genotype-matched phenotypically wild type pups. Mean ± SD body weights of affected pups were 95 ± 8% of control values at e16 and 73 ± 7% at e18. There were no differences in areas under the maternal ipGTT curves at either e16 (mean ± SD being 99.0 ± 9.1% of control values; P=.9 or e18 (91.4 ± 13.4%; P=.3, suggesting that effects on transplacental glucose transport in these mice are not mediated through changes in maternal glucose concentrations.

  2. CONTAMINANT-ASSOCIATED ENDOCRINE DISRUPTION IN REPTILES.

    Science.gov (United States)

    The data presented suggest that contaminants can alter the endocrine and reproductive system of reptiles by mimicking hormones and by various mechanisms other than direct hormonal mimicry. However, these data indicate, as do many other studies using various vertebrates, that a fo...

  3. Mastitis associated transcriptomic disruptions in cattle

    Science.gov (United States)

    Mastitis is ranked as the top disease for dairy cattle based on traditional cost analysis. Greater than 100 organisms from a broad phylogenetic spectrum are able to cause bovine mastitis. Transcriptomic characterization facilitates our understanding of host-pathogen relations and provides mechanisti...

  4. Neonicotinoid insecticide residues in soil dust and associated parent soil in fields with a history of seed treatment use on crops in southwestern Ontario.

    Science.gov (United States)

    Limay-Rios, Victor; Forero, Luis Gabriel; Xue, Yingen; Smith, Jocelyn; Baute, Tracey; Schaafsma, Arthur

    2016-02-01

    Using neonicotinoid insecticides as seed treatments is a common practice in field crop production. Exposure of nontarget organisms to neonicotinoids present in various environmental matrices is debated. In the present study, concentrations of neonicotinoid residues were measured in the top 5 cm of soil and overlying soil surface dust before planting in 25 commercial fields with a history of neonicotinoid seed treatment use in southwestern Ontario in 2013 and 2014 using liquid chromatography-electrospray ionization tandem mass spectrometry. The mean total concentrations were 3.05 ng/g and 47.84 ng/g in 2013 and 5.59 ng/g and 71.17 ng/g in 2014 for parent soil and soil surface dust, respectively. When surface and parent soil residues were compared the mean concentration in surface dust was 15.6-fold and 12.7-fold higher than that in parent soil in 2013 and 2014, respectively. Pooled over years, the surface dust to parent soil ratio was 13.7, with mean concentrations of 4.36 ng/g and 59.86 ng/g for parent soil and surface dust, respectively. The present study's results will contribute important knowledge about the role these residues may play in the overall risk assessment currently under way for the source, transport, and impact of neonicotinoid insecticide residues in a maize ecosystem. © 2015 SETAC.

  5. Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

    Science.gov (United States)

    Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

    2018-02-27

    The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

  6. Ultrasonic disruption of algae cells

    Science.gov (United States)

    King, P. M.; Nowotarski, K.; Joyce, E. M.; Mason, T. J.

    2012-05-01

    During last decade there has been increasing interest in the production of sustainable fuels from microalgae (R.H. Wijffels and M.J. Barbosa, 2010; Singh et al 2011; D.H. Lee 2011). The aim of this project was to determine if algal cells can be ultrasonically disrupted to release lipids for biofuel production. Ultrasonic disruption of two unicellular algal species: Dunnaliella salina and Nannochloropsis oculata was investigated using a 20 kHz probe. Haemocytometer, optical density, UV-Vis, fluoro-spectrophotometer and confocal microscopy results demonstrated complete cell destruction of Dunaliella salina within 16 minutes of sonication. Results obtained for Nannochloropsis oculata differed in that ultrasound dispersed clumped cells with little or no cell disruption, as observed by haemocytometer and confocal microscopy analysis. However, UV-Visible and fluoro-spectrophotometer analysis indicated chlorophyll release following sonication, suggesting some cell disruption had occurred.

  7. A Network Disruption Modeling Tool

    National Research Council Canada - National Science Library

    Leinart, James

    1998-01-01

    Given that network disruption has been identified as a military objective and C2-attack has been identified as the mechanism to accomplish this objective, a target set must be acquired and priorities...

  8. Enzymatic cell disruption of microalgae biomass in biorefinery processes.

    Science.gov (United States)

    Demuez, Marie; Mahdy, Ahmed; Tomás-Pejó, Elia; González-Fernández, Cristina; Ballesteros, Mercedes

    2015-10-01

    When employing biotechnological processes for the procurement of biofuels and bio-products from microalgae, one of the most critical steps affecting economy and yields is the "cell disruption" stage. Currently, enzymatic cell disruption has delivered effective and cost competitive results when compared to mechanical and chemical cell disruption methods. However, the introduction of enzymes implies additional associated cost within the overall process. In order to reduce this cost, autolysis of microalgae is proposed as alternative enzymatic cell disruption method. This review aims to provide the state of the art of enzymatic cell disruption treatments employed in biorefinery processes and highlights the use of endopeptidases. During the enzymatic processes of microalgae life cycle, some lytic enzymes involved in cell division and programmed cell death have been proven useful in performing cell lysis. In this context, the role of endopeptidases is emphasized. Mirroring these natural events, an alternative cell disruption approach is proposed and described with the potential to induce the autolysis process using intrinsic cell enzymes. Integrating induced autolysis within biofuel production processes offers a promising approach to reduce overall global costs and energetic input associated with those of current cell disruption methods. A number of options for further inquiry are also discussed. © 2015 Wiley Periodicals, Inc.

  9. Disruptive innovation: the demand side.

    Science.gov (United States)

    Havighurst, Clark C

    2008-01-01

    The notion of disruptive innovation provides a welcome framework for considering the prospects for low-cost alternatives in American medicine. Such innovations as have been seen, however, are largely the result of demand by patients paying their own bills because they have high-deductible coverage or are uninsured. Many other cost-saving innovations are discouraged by financing systems that are themselves largely immune to competition from disruptive innovators.

  10. Identification of the minimal functional unit in the low density lipoprotein receptor-related protein for binding the receptor-associated protein (RAP). A conserved acidic residue in the complement-type repeats is important for recognition of RAP.

    Science.gov (United States)

    Andersen, O M; Christensen, L L; Christensen, P A; Sørensen, E S; Jacobsen, C; Moestrup, S K; Etzerodt, M; Thogersen, H C

    2000-07-14

    The low density lipoprotein receptor-related protein (LRP), a member of the low density lipoprotein receptor family, mediates the internalization of a diverse set of ligands. The ligand binding sites are located in different regions of clusters consisting of approximately 40 residues, cysteine-rich complement-type repeats (CRs). The 39-40-kDa receptor-associated protein, a folding chaperone/escort protein required for efficient transport of functional LRP to the cell surface, is an antagonist of all identified ligands. To analyze the multisite inhibition by RAP in ligand binding of LRP, we have used an Escherichia coli expression system to produce fragments of the entire second ligand binding cluster of LRP (CR3-10). By ligand affinity chromatography and surface plasmon resonance analysis, we show that RAP binds to all two-repeat modules except CR910. CR10 differs from other repeats in cluster II by not containing a surface-exposed conserved acidic residue between Cys(IV) and Cys(V). By site-directed mutagenesis and ligand competition analysis, we provide evidence for a crucial importance of this conserved residue for RAP binding. We provide experimental evidence showing that two adjacent complement-type repeats, both containing a conserved acidic residue, represent a minimal unit required for efficient binding to RAP.

  11. Neural net prediction of tokamak plasma disruptions

    International Nuclear Information System (INIS)

    Hernandez, J.V.; Lin, Z.; Horton, W.; McCool, S.C.

    1994-10-01

    The computation based on neural net algorithms in predicting minor and major disruptions in TEXT tokamak discharges has been performed. Future values of the fluctuating magnetic signal are predicted based on L past values of the magnetic fluctuation signal, measured by a single Mirnov coil. The time step used (= 0.04ms) corresponds to the experimental data sampling rate. Two kinds of approaches are adopted for the task, the contiguous future prediction and the multi-timescale prediction. Results are shown for comparison. Both networks are trained through the back-propagation algorithm with inertial terms. The degree of this success indicates that the magnetic fluctuations associated with tokamak disruptions may be characterized by a relatively low-dimensional dynamical system

  12. Emotions, cognitive interference, and concentration disruption in youth sport.

    Science.gov (United States)

    McCarthy, Paul J; Allen, Mark S; Jones, Marc V

    2013-01-01

    We explored the relationship between emotions, cognitive interference, concentration disruption and performance in youth sport. In study 1, 150 youth sport athletes (Mage = 13.13 years, s = 1.79) completed measures of emotion, cognitive interference, and concentration disruption for their most recently completed competition. In Study 2, 46 female rhythmic gymnasts (Mage = 10.30 years, s = 1.74) completed measures of emotion immediately before competition, and measures of cognitive interference and concentration disruption immediately after competition. Study 1 showed that anxiety and dejection were associated with more interfering thoughts and greater disruptions in concentration, whereas the effects of anger and happiness on interfering thoughts differed relative to the age of participants. Specifically, anger was associated with more interfering thoughts only in younger athletes and happiness was associated with fewer interfering thoughts only in older athletes. Study 2 showed that emotions experienced before competition were not strongly associated with cognitive interference or concentration disruption, but athletes reporting more thoughts of escape in competition were less successful in the competition as measured by objective performance scores. These findings demonstrate that emotions are important for cognitive interference and concentration disruption, and provide some initial evidence that cognitive interference is important for performance in youth sport.

  13. Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: cytokine and gene therapy with IL-2 and GM-CSF

    Czech Academy of Sciences Publication Activity Database

    Mikyšková, Romana; Indrová, Marie; Šímová, Jana; Jandlová, Táňa; Bieblová, Jana; Jinoch, P.; Bubeník, Jan; Vonka, V.

    2004-01-01

    Roč. 24, č. 1 (2004), s. 161-167 ISSN 1019-6439 R&D Projects: GA MZd NC7148; GA MZd NC7552; GA ČR GA301/01/0985 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 * gene therapy * minimal residual tumour disease Subject RIV: FD - Oncology ; Hematology Impact factor: 3.056, year: 2004

  14. Genetically modified cellular vaccines against human papillomavirus type 16 (HPV16)-associated tumors: adjuvant treatment of minimal residual disease after surgery/chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Šímová, Jana

    2009-01-01

    Roč. 14, č. 1 (2009), s. 169-173 ISSN 1107-0625 R&D Projects: GA ČR GA301/06/0774; GA ČR GA301/07/1410 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Keywords : residual tumour disease * HPV 16 * cellular vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.600, year: 2009

  15. Analysis of the spallation residues and the associated particles in the reaction Fe+p at 1 GeV per nucleon

    International Nuclear Information System (INIS)

    Le Gentil, E.

    2006-09-01

    SPALADIN is a new type of spallation experiment that has been carried out at the GSI accelerator facility (Germany) in order to improve the modelling of the spallation reaction. This experiment is based on the coincidence measurement in inverse kinematics of the spallation residues and the de-excitation fragments. This work presents the analysis of Fe 56 + p reaction at 1 GeV per nucleon. Results on cross-sections and heavy residue velocity spectra are compared to previous data and enabled us to characterize the setup. Most of the element production cross-sections have been obtained with an uncertainty below 10 per cent. In the particular case of helium, its production cross-section has been measured to be σ(1 GeV) = (598 ± 67) mb. The knowledge of this cross-section is important to assess the irradiation damage undergone by the window separating the accelerator from the target. The study of the de-excitation of the pre-fragment shows that the evaporation of light particles (Z ≤ 2) is the main way of de-excitation whatever the collision centrality. However, the de-excitation through the emission of intermediate mass fragments is observed in 5% of the events and most of these events correspond to a very asymmetric binary breaking. The velocity distributions of light residues (with regards to the mass of the projectile) show a significant disagreement with the average velocities predicted by spallation codes. (A.C.)

  16. Combinatorial construction of toric residues

    OpenAIRE

    Khetan, Amit; Soprounov, Ivan

    2004-01-01

    The toric residue is a map depending on n+1 semi-ample divisors on a complete toric variety of dimension n. It appears in a variety of contexts such as sparse polynomial systems, mirror symmetry, and GKZ hypergeometric functions. In this paper we investigate the problem of finding an explicit element whose toric residue is equal to one. Such an element is shown to exist if and only if the associated polytopes are essential. We reduce the problem to finding a collection of partitions of the la...

  17. A Three-Year Follow-Up Study of Antibiotic and Metal Residues, Antibiotic Resistance and Resistance Genes, Focusing on Kshipra-A River Associated with Holy Religious Mass-Bathing in India: Protocol Paper.

    Science.gov (United States)

    Diwan, Vishal; Purohit, Manju; Chandran, Salesh; Parashar, Vivek; Shah, Harshada; Mahadik, Vijay K; Stålsby Lundborg, Cecilia; Tamhankar, Ashok J

    2017-05-29

    Antibiotic resistance (ABR) is one of the major health emergencies for global society. Little is known about the ABR of environmental bacteria and therefore it is important to understand ABR reservoirs in the environment and their potential impact on health. Quantitative and qualitative data will be collected during a 3-year follow-up study of a river associated with religious mass-bathing in Central India. Surface-water and sediment samples will be collected from seven locations at regular intervals for 3 years during religious mass-bathing and in absence of it to monitor water-quality, antibiotic residues, resistant bacteria, antibiotic resistance genes and metals. Approval has been obtained from the Ethics Committee of R.D. Gardi Medical College, Ujjain, India (No. 2013/07/17-311). The results will address the issue of antibiotic residues and antibiotic resistance with a focus on a river environment in India within a typical socio-behavioural context of religious mass-bathing. It will enhance our understanding about the relationship between antibiotic residue levels, water-quality, heavy metals and antibiotic resistance patterns in Escherichia coli isolated from river-water and sediment, and seasonal differences that are associated with religious mass-bathing. We will also document, identify and clarify the genetic differences/similarities relating to phenotypic antibiotic resistance in bacteria in rivers during religious mass-bathing or during periods when there is no mass-bathing.

  18. A Three-Year Follow-Up Study of Antibiotic and Metal Residues, Antibiotic Resistance and Resistance Genes, Focusing on Kshipra—A River Associated with Holy Religious Mass-Bathing in India: Protocol Paper

    Science.gov (United States)

    Diwan, Vishal; Purohit, Manju; Chandran, Salesh; Parashar, Vivek; Shah, Harshada; Mahadik, Vijay K.; Stålsby Lundborg, Cecilia; Tamhankar, Ashok J.

    2017-01-01

    Background: Antibiotic resistance (ABR) is one of the major health emergencies for global society. Little is known about the ABR of environmental bacteria and therefore it is important to understand ABR reservoirs in the environment and their potential impact on health. Method/Design: Quantitative and qualitative data will be collected during a 3-year follow-up study of a river associated with religious mass-bathing in Central India. Surface-water and sediment samples will be collected from seven locations at regular intervals for 3 years during religious mass-bathing and in absence of it to monitor water-quality, antibiotic residues, resistant bacteria, antibiotic resistance genes and metals. Approval has been obtained from the Ethics Committee of R.D. Gardi Medical College, Ujjain, India (No. 2013/07/17-311). Results: The results will address the issue of antibiotic residues and antibiotic resistance with a focus on a river environment in India within a typical socio-behavioural context of religious mass-bathing. It will enhance our understanding about the relationship between antibiotic residue levels, water-quality, heavy metals and antibiotic resistance patterns in Escherichia coli isolated from river-water and sediment, and seasonal differences that are associated with religious mass-bathing. We will also document, identify and clarify the genetic differences/similarities relating to phenotypic antibiotic resistance in bacteria in rivers during religious mass-bathing or during periods when there is no mass-bathing. PMID:28555050

  19. A Three-Year Follow-Up Study of Antibiotic and Metal Residues, Antibiotic Resistance and Resistance Genes, Focusing on Kshipra—A River Associated with Holy Religious Mass-Bathing in India: Protocol Paper

    Directory of Open Access Journals (Sweden)

    Vishal Diwan

    2017-05-01

    Full Text Available Background: Antibiotic resistance (ABR is one of the major health emergencies for global society. Little is known about the ABR of environmental bacteria and therefore it is important to understand ABR reservoirs in the environment and their potential impact on health. Method/Design: Quantitative and qualitative data will be collected during a 3-year follow-up study of a river associated with religious mass-bathing in Central India. Surface-water and sediment samples will be collected from seven locations at regular intervals for 3 years during religious mass-bathing and in absence of it to monitor water-quality, antibiotic residues, resistant bacteria, antibiotic resistance genes and metals. Approval has been obtained from the Ethics Committee of R.D. Gardi Medical College, Ujjain, India (No. 2013/07/17-311. Results: The results will address the issue of antibiotic residues and antibiotic resistance with a focus on a river environment in India within a typical socio-behavioural context of religious mass-bathing. It will enhance our understanding about the relationship between antibiotic residue levels, water-quality, heavy metals and antibiotic resistance patterns in Escherichia coli isolated from river-water and sediment, and seasonal differences that are associated with religious mass-bathing. We will also document, identify and clarify the genetic differences/similarities relating to phenotypic antibiotic resistance in bacteria in rivers during religious mass-bathing or during periods when there is no mass-bathing.

  20. Disruption studies on ASDEX upgrade

    International Nuclear Information System (INIS)

    Pautasso, G.; Egorov, S.; Finken, K.H.

    2003-01-01

    Disruptions generate large thermal and mechanical stresses on the tokamak components and are occasionally responsible for damages to the machine. For a future reactor disruptions have a significant impact on the design since all loading conditions must be analyzed in accordance with stricter design criteria (due to safety or difficult maintenance). Therefore the uncertainties affecting the predicted stresses must be reduced as much as possible with a more comprehensive set of measurements and analyses in this generation of experimental machines, and avoidance/predictive methods must be developed further. Disruption studies on ASDEX Upgrade are focused on these subjects, namely on: (1) understanding the physical mechanisms leading to this phenomenon in order to learn to avoid it or to predict its occurrence and to mitigate its effects; (2) analyzing the effects of disruptions on the machine to determine the functional dependence of the thermal and mechanical loads upon the discharge parameters. This allows, firstly, to dimension or reinforce the machine components to withstand these loads and, secondly, to extrapolate them to tokamaks still in the design phase; (3) learning to mitigate the consequence of disruptions, i.e. thermal loads, mechanical forces and runaways with injection of impurity pellets or gas. This paper is focused on most recent results concerning points, i.e. on the analysis of the degree of asymmetry of the forces and on the use of impurity puff for mitigation

  1. Natural Hazards and Supply Chain Disruptions

    Science.gov (United States)

    Haraguchi, M.

    2016-12-01

    Natural hazards distress the global economy through disruptions in supply chain networks. Moreover, despite increasing investment to infrastructure for disaster risk management, economic damages and losses caused by natural hazards are increasing. Manufacturing companies today have reduced inventories and streamlined logistics in order to maximize economic competitiveness. As a result, today's supply chains are profoundly susceptible to systemic risks, which are the risk of collapse of an entire network caused by a few node of the network. For instance, the prolonged floods in Thailand in 2011 caused supply chain disruptions in their primary industries, i.e. electronic and automotive industries, harming not only the Thai economy but also the global economy. Similar problems occurred after the Great East Japan Earthquake and Tsunami in 2011, the Mississippi River floods and droughts during 2011 - 2013, and the Earthquake in Kumamoto Japan in 2016. This study attempts to discover what kind of effective measures are available for private companies to manage supply chain disruptions caused by floods. It also proposes a method to estimate potential risks using a Bayesian network. The study uses a Bayesian network to create synthetic networks that include variables associated with the magnitude and duration of floods, major components of supply chains such as logistics, multiple layers of suppliers, warehouses, and consumer markets. Considering situations across different times, our study shows desirable data requirements for the analysis and effective measures to improve Value at Risk (VaR) for private enterprises and supply chains.

  2. Disruptive event analysis: volcanism and igneous intrusion

    International Nuclear Information System (INIS)

    Crowe, B.M.

    1979-01-01

    Three basic topics are addressed for the disruptive event analysis: first, the range of disruptive consequences of a radioactive waste repository by volcanic activity; second, the possible reduction of the risk of disruption by volcanic activity through selective siting of a repository; and third, the quantification of the probability of repository disruption by volcanic activity

  3. Online Education Cast as "Disruptive Innovation"

    Science.gov (United States)

    Totter, Andrew

    2008-01-01

    Technology-based forces of "disruptive innovation" are gathering around public education and will overhaul the way K-12 students learn--with potentially dramatic consequences for established public schools, according to an upcoming book that draws parallels to disruptions in other industries. In his "Disrupting Class: How Disruptive Innovation…

  4. Residuals Management and Water Pollution Control Planning.

    Science.gov (United States)

    Environmental Protection Agency, Washington, DC. Office of Public Affairs.

    This pamphlet addresses the problems associated with residuals and water quality especially as it relates to the National Water Pollution Control Program. The types of residuals and appropriate management systems are discussed. Additionally, one section is devoted to the role of citizen participation in developing management programs. (CS)

  5. Poor quality of life, depressed mood, and memory impairment may be mediated by sleep disruption in patients with Addison's disease.

    Science.gov (United States)

    Henry, Michelle; Wolf, Pedro S A; Ross, Ian L; Thomas, Kevin G F

    2015-11-01

    Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. In fact, hydrocortisone replacement in AD patients likely induces disrupted sleep. Given that healthy sleep plays an important role in improving quality of life, optimizing cognition, and ensuring affect regulation, the aim of this study was to investigate whether poor quality of life, mood alterations, and memory complaints reported by AD patients are associated with their disrupted sleep patterns. Sixty patients with AD and 60 matched healthy controls completed a battery of self-report questionnaires assessing perceived physical and mental health (Short-Form 36), mood (Beck Depression Inventory-II), sleep quality (Pittsburgh Sleep Quality Index), and cognition (Cognitive Failures Questionnaire). A latent variable model revealed that although AD had a significant direct effect on quality of life, the indirect effect of sleep was significantly greater. Furthermore, although AD had no direct effect on cognitive functioning, the indirect effect of sleep was significant. The overall model showed a good fit (comparative fit index = 0.91, root mean square of approximation = 0.09, and standardized root mean square residual = 0.05). Our findings suggest that disrupted sleep, and not the disease per se, may induce poor quality of life, memory impairment, and affect dysregulation in patients with AD. We think that improving sleep architecture may improve cognitive, affective, and physical functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Professional Disruption in Health Regulation

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob

    2016-01-01

    How do professions respond to fast-moving technological changes? Disruptive innovations overturn expectations about how markets function and develop, and they often raise moral, legal and scientific concerns among professionals. Sudden technological changes can result in a state of professional...... disruption, in which technological change challenges the institutional arrangements of a profession. This article distinguishes between fast and slow processes of professional change, focusing on the role of technology as one cause of fast changes to a profession. Professionals and non-professionals engage...... in framing contests that draw on cognitive, normative and relational keys to signal their expectations. It is in these framing contests that professionals run the risk of disruption. Drawing on interview data with key policy actors, I investigate electronic cigarettes regulation in the European Union and its...

  7. Major plasma disruptions in TNS

    International Nuclear Information System (INIS)

    Onega, R.J.; Becraft, W.R.; Bettis, E.S.

    1979-02-01

    Evaluation of the instrumentation and control of a power producing tokamak fusion reactor such as The Next Step (TNS) requires an assessment of the consequences of a major plasma disruption during reactor operation. The most important consequence of a disruption will be damage to the first wall from thermal and magnetic stress. Severe temperature gradients will cause thermal stress, placing a limit on the number of disruptions that can occur before the integrity of the wall is lost, and eddy currents induced in the wall will interact with the magnetic energy of the plasma and the →B/sub T/ field to create mechanical forces. Consequences to the ohmic heating (OH) coils, their power supplies, and other coils must also be taken into account

  8. Disrupting the Industry with Play

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop

    2016-01-01

    or two ago. This is significantly disrupting the industry in several market sectors. This paper describes the components of the playware and embodied artificial intelligence research that has led to disruption in the industrial robotics sector, and which points to the next disruption of the health care......Decades of research into intelligent, playful technology and user-friendly man-machine interfaces has provided important insight into the creation of robotic systems and intelligent interactive systems which are much more user-friendly, safer and cheaper than what appeared possible merely a decade...... sector. This includes playful robotics, LEGO robots for kids, minimal robot systems, user-friendly, behavior-based, biomimetic, modular robotics and intelligent systems. The insight into these components and the use in synthesis for designing robots and intelligent systems allows anybody, anywhere...

  9. Novel peptide for attenuation of hyperoxia-induced disruption of lung endothelial barrier and pulmonary edema via modulating peroxynitrite formation.

    Science.gov (United States)

    Kondrikov, Dmitry; Gross, Christine; Black, Stephen M; Su, Yunchao

    2014-11-28

    Pulmonary damages of oxygen toxicity include vascular leakage and pulmonary edema. We have previously reported that hyperoxia increases the formation of NO and peroxynitrite in lung endothelial cells via increased interaction of endothelial nitric oxide (eNOS) with β-actin. A peptide (P326TAT) with amino acid sequence corresponding to the actin binding region of eNOS residues 326-333 has been shown to reduce the hyperoxia-induced formation of NO and peroxynitrite in lung endothelial cells. In the present study, we found that exposure of pulmonary artery endothelial cells to hyperoxia (95% oxygen and 5% CO2) for 48 h resulted in disruption of monolayer barrier integrity in two phases, and apoptosis occurred in the second phase. NOS inhibitor N(G)-nitro-L-arginine methyl ester attenuated the endothelial barrier disruption in both phases. Peroxynitrite scavenger uric acid did not affect the first phase but ameliorated the second phase of endothelial barrier disruption and apoptosis. P326TAT inhibited hyperoxia-induced disruption of monolayer barrier integrity in two phases and apoptosis in the second phase. More importantly, injection of P326TAT attenuated vascular leakage, pulmonary edema, and endothelial apoptosis in the lungs of mice exposed to hyperoxia. P326TAT also significantly reduced the increase in eNOS-β-actin association and protein tyrosine nitration. Together, these results indicate that peptide P326TAT ameliorates barrier dysfunction of hyperoxic lung endothelial monolayer and attenuates eNOS-β-actin association, peroxynitrite formation, endothelial apoptosis, and pulmonary edema in lungs of hyperoxic mice. P326TAT can be a novel therapeutic agent to treat or prevent acute lung injury in oxygen toxicity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Radiological impact on the workers, members of the public, and environment from the partial decommissioning of Pakistan Research Reactor-I and its associated radioactive residues.

    Science.gov (United States)

    Ali, A; Orfi, S D; Manzur, H; Aslam, M

    2001-05-01

    The Pakistan Research Reactor-I (PARR-I) is a swimming pool type research reactor originally designed and built for a thermal power of 5 MW using High Enriched Uranium (HEU) fuel. In 1990-1991 the reactor was redesigned, partially decommissioned and recommissioned to operate with Low Enriched Uranium (LEU) fuel at a thermal power of 10 MW. An essential requirement, construction and commissioning of a wet spent fuel storage bay and fabrication of an irradiated fuel transfer cask were completed before actual dismantling of the reactor core. During the partial decommissioning operations, radioactive waste generated included 600 m3 low-level liquid radioactive waste and 14 m3 of solid radioactive waste with an average specific activity of 4.52 Bq ml(-1) and 2.22 kBq g(-1), respectively. External radiation doses of the workers were determined using TLD (NG 6,7) and direct reading dosimeters. The maximum individual external radiation dose received by any worker during this practice was 5 mSv, which was 25% of the annual dose limit of 20 mSv. Detection and measurement of internal contamination was carried out using bioassay techniques. During the whole operation, not a single case of internal contamination was detected. The ambient radiation levels around waste seepage pits are periodically monitored using TLD (G-2 cards) and G. M. radiation survey meters. Underground migration of radioactivity is checked by analyzing seepage water samples taken from boreholes that have been dug at different locations in the vicinity of the radioactive residues. The monitoring around disposal sites containing radioactive residues has been continued during the last 9 y and will be continued in the future. So far, no rise in the environmental gamma radiation dose level and migration of underground radionuclides has been found in the vicinity of these disposal sites. Working personal during the decommissioning of PARR-I have been found to be radiologically safe. Adherence to the ALARA

  11. Disruptive Innovation in Healthcare & Rehabilitation

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2014-01-01

    Disruption is a powerful body of theory that describes how people interact and react, how behavior is shaped, how organizational cultures form and influence decisions. Innovation is the process of translating an idea or invention into a product or service that creates value or for which customers...... will pay. Disruptive Innovation in context of the author’s body of work in healthcare and rehabilitation relates to how development of a cloud-based converged infrastructure resource, similar to that conceived in a national (Danish) study titled Humanics, can act as an accessible data and knowledge...

  12. Elevated vacuum suspension preserves residual-limb skin health in people with lower-limb amputation: Randomized clinical trial.

    Science.gov (United States)

    Rink, Cameron; Wernke, Matthew M; Powell, Heather M; Gynawali, Surya; Schroeder, Ryan M; Kim, Jayne Y; Denune, Jeffrey A; Gordillo, Gayle M; Colvin, James M; Sen, Chandan K

    2016-01-01

    A growing number of clinical trials and case reports support qualitative claims that use of an elevated vacuum suspension (EVS) prosthesis improves residual-limb health on the basis of self-reported questionnaires, clinical outcomes scales, and wound closure studies. Here, we report first efforts to quantitatively assess residual-limb circulation in response to EVS. Residual-limb skin health and perfusion of people with lower-limb amputation (N = 10) were assessed during a randomized crossover study comparing EVS with nonelevated vacuum suspension (control) over a 32 wk period using noninvasive probes (transepidermal water loss, laser speckle imaging, transcutaneous oxygen measurement) and functional hyperspectral imaging approaches. Regardless of the suspension system, prosthesis donning decreased perfusion in the residual limb under resting conditions. After 16 wk of use, EVS improved residual-limb oxygenation during treadmill walking. Likewise, prosthesis-induced reactive hyperemia was attenuated with EVS following 16 wk of use. Skin barrier function was preserved with EVS but disrupted after control socket use. Taken together, outcomes suggest chronic EVS use improves perfusion and preserves skin barrier function in people with lower-limb amputation. ClinicalTrials.gov; "Evaluation of limb health associated with a prosthetic vacuum socket system": NCT01839123; https://clinicaltrials.gov/ct2/show/NCT01839123?term=NCT01839123&rank=1.

  13. Residual gas analysis

    International Nuclear Information System (INIS)

    Berecz, I.

    1982-01-01

    Determination of the residual gas composition in vacuum systems by a special mass spectrometric method was presented. The quadrupole mass spectrometer (QMS) and its application in thin film technology was discussed. Results, partial pressure versus time curves as well as the line spectra of the residual gases in case of the vaporization of a Ti-Pd-Au alloy were demonstrated together with the possible construction schemes of QMS residual gas analysers. (Sz.J.)

  14. JET and COMPASS asymmetrical disruptions

    Czech Academy of Sciences Publication Activity Database

    Gerasimov, S.N.; Abreu, P.; Baruzzo, M.; Drozdov, V.; Dvornova, A.; Havlíček, Josef; Hender, T.C.; Hronová-Bilyková, Olena; Kruezi, U.; Li, X.; Markovič, Tomáš; Pánek, Radomír; Rubinacci, G.; Tsalas, M.; Ventre, S.; Villone, F.; Zakharov, L.E.

    2015-01-01

    Roč. 55, č. 11 (2015), s. 113006-113006 ISSN 0029-5515 R&D Projects: GA MŠk(CZ) LM2011021 Institutional support: RVO:61389021 Keywords : tokamak * asymmetrical disruption * JET * COMPASS Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 4.040, year: 2015

  15. Disruption mitigation on Tore Supra

    International Nuclear Information System (INIS)

    Martin, G.; Sourd, F.; Saint-Laurent, F.; Bucalossi, J.; Eriksson, L.G.

    2004-01-01

    During disruptions, the plasma energy is lost on the first wall within 1 ms, forces up to hundred tons are applied to the structures and kA of electrons are accelerated up to 50 MeV (runaway electrons). Already sources of concern in present day tokamaks, extrapolation to ITER shows the necessity of mitigation procedures, to avoid serious damages to in-vessel components. Massive gas injection was proposed, and encouraging tests have been done on Textor and DIII-D. Similar experiments where performed on Tore Supra, with the goal to validate their effect on runaway electrons, observed during the majority of disruptions. 0.1 mole of helium was injected within 5 ms in ohmic plasmas, up to 1.2 MA, either stable, or in a pre-disruptive phase (argon puffing). Beneficial effects where obtained: reduction of the current fall rate and eddy currents, total disappearance of runaway electrons and easy recovery for the next pulse, without noticeable helium pollution of following plasmas. Analysis of the 4 ms period between injection and disruption indicates that to reach these goals, one need to inject enough helium to keep it only partially ionised. It corresponds to 0.1 g for Tore Supra, and extrapolate to hundreds of grams for ITER. (authors)

  16. Jogging Can Modify Disruptive Behaviors.

    Science.gov (United States)

    Allen, Jill I.

    1980-01-01

    Jogging was used to modify disruptive behavior as part of the classroom routine for 12 learning disabled elementary-grade boys. The number of incidents of each of five negative behaviors were reduced by half following the 10-minute jogging routine. (SBH)

  17. Will blockchain disrupt your business?

    OpenAIRE

    Schmeiss, Jessica

    2018-01-01

    Blockchain has been praised to be “the technology most likely to change the next decade of business”. The disruptive power of the blockchain technology is yet limited, says HIIG-researcher Jessica Schmeiss. Beyond the hype, there a opportunities for companies to make their current business models more cost-effective and more efficient.

  18. Marital Alternatives and Marital Disruption.

    Science.gov (United States)

    Udry, J. Richard

    1981-01-01

    Explores the usefulness of "marital alternatives" as a dimension in explaining marital stability, using longitudinal data from a panel of married, White, urban couples from 16 urban areas. Results indicated the dimension of marital alternatives appeared to be a better predictor of marital disruption than marital satisfaction. (Author/RC)

  19. Disruption mitigation on Tore Supra

    International Nuclear Information System (INIS)

    Martin, G.; Sourd, F.; Saint-Laurent, F.; Bucalossi, J.; Eriksson, L.G.

    2005-01-01

    During disruptions, the plasma energy is lost on the first wall within 1 ms, forces up to hundred tons are applied to the structures and kA of electrons are accelerated up to 50 MeV (runaway electrons). Already sources of concern in present day tokamaks, extrapolation to ITER shows the necessity of mitigation procedures, to avoid serious damages to in-vessel components. Massive gas injection was proposed, and encouraging tests have been done on Textor and DIII-D. Similar experiments where performed on Tore Supra, with the goal to validate their effect on runaway electrons, observed during the majority of disruptions. 0.1 mole of helium was injected within 5 ms in ohmic plasmas, up to 1.2 MA, either stable, or in a pre-disruptive phase (argon puffing). Beneficial effects where obtained: reduction of the current fall rate and eddy currents, total disappearance of runaway electrons and easy recovery for the next pulse, without noticeable helium pollution of following plasmas. Analysis of the 4 ms period between injection and disruption indicates that to reach these goals, one need to inject enough helium to keep it only partially ionised. It correspond to 0.1 g for Tore Supra, and extrapolate to hundred's of grams for ITER. (author)

  20. Short- and long-term health consequences of sleep disruption

    Directory of Open Access Journals (Sweden)

    Medic G

    2017-05-01

    Full Text Available Goran Medic,1,2 Micheline Wille,1 Michiel EH Hemels1 1Market Access, Horizon Pharma B.V., Utrecht, 2Unit of Pharmacoepidemiology & Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands Abstract: Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep. Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic–pituitary–adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with

  1. Supply disruption cost for power network planning

    International Nuclear Information System (INIS)

    Kjoelle, G.H.

    1992-09-01

    A description is given of the method of approach to calculate the total annual socio-economic cost of power supply disruption and non-supplied energy, included the utilities' cost for planning. The total socio-economic supply disruption cost is the sum of the customers' disruption cost and the utilities' cost for failure and disruption. The mean weighted disruption cost for Norway for one hour disruption is NOK 19 per kWh. The customers' annual disruption cost is calculated with basis in the specific disruption cost referred to heavy load (January) and dimensioning maximum loads. The loads are reduced by factors taking into account the time variations of the failure frequency, duration, the loads and the disruption cost. 6 refs

  2. Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual β-cell function 1 year after diagnosis of type 1 diabetes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise Max; Rasmussen, Morten Arendt; Pörksen, Sven

    2013-01-01

    The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes...... related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual β-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration...

  3. Effect of an acrylic terpolymer barrier film beneath transparent catheter dressings on skin integrity, risk of dressing disruption, catheter colonisation and infection.

    Science.gov (United States)

    Pivkina, A I; Gusarov, V G; Blot, S I; Zhivotneva, I V; Pasko, N V; Zamyatin, M N

    2018-03-23

    We assessed the effect of a skin-protective terpolymer barrier film around the catheter insertion site on frequency of dressing disruptions and skin integrity issues (hyperaemia, skin irritation, residues of adhesives and moisture under the dressing). Secondary outcomes included colonisation of the central venous catheter (CVC) and rates of central line-associated bloodstream infection. A monocentric, open-label, randomised controlled trial was performed comparing a control group receiving standard transparent catheter dressings without the skin-protecting barrier film and an intervention group receiving a transparent chlorhexidine-impregnated dressing with use of the skin-protective acrylic terpolymer barrier film (3M™ Cavilon™ No - Sting Barrier Film, 3 M Health Care, St. Paul, MN, USA). Sixty patients were enrolled and randomised in the study accounting for 60 central venous catheters and a total of 533 catheter days. Dressing disruptions occurred more frequently and at sooner time point in the control group. Skin integrity issues were significantly less observed in the intervention group. No differences in CVC colonisation or central line-associated bloodstream infection were observed. The application of a barrier film creating a skin-protective polymer layer beneath transparent catheter dressings is associated with less dressing disruptions and skin integrity issues without altering the risk of infectious complications if used in combination with a chlorhexidine-impregnated catheter dressing. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Disruption of dark matter substructure: fact or fiction?

    Science.gov (United States)

    van den Bosch, Frank C.; Ogiya, Go; Hahn, Oliver; Burkert, Andreas

    2018-03-01

    Accurately predicting the demographics of dark matter (DM) substructure is of paramount importance for many fields of astrophysics, including gravitational lensing, galaxy evolution, halo occupation modelling, and constraining the nature of DM. Because of its strongly non-linear nature, DM substructure is typically modelled using N-body simulations, which reveal that large fractions of DM subhaloes undergo complete disruption. In this paper, we use both analytical estimates and idealized numerical simulations to investigate whether this disruption is mainly physical, due to tidal heating and stripping, or numerical (i.e. artificial). We show that, contrary to naive expectation, subhaloes that experience a tidal shock ΔE that exceeds the subhalo's binding energy, |Eb|, do not undergo disruption, even when ΔE/|Eb| is as large as 100. Along the same line, and contrary to existing claims in the literature, instantaneously stripping matter from the outskirts of a DM subhalo also does not result in its complete disruption, even when the instantaneous remnant has positive binding energy. In addition, we show that tidal heating due to high-speed (impulsive) encounters with other subhaloes (`harassment') is negligible compared to the tidal effects due to the host halo. Hence, we conclude that, in the absence of baryonic processes, the complete physical disruption of CDM substructure is extremely rare and that most disruption in numerical simulations therefore must be artificial. We discuss various processes that have been associated with numerical overmerging and conclude that inadequate force softening is the most likely culprit.

  5. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

    Science.gov (United States)

    Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

    2015-08-01

    In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

  6. Agricultural pesticide residues

    International Nuclear Information System (INIS)

    Fuehr, F.

    1984-01-01

    The utilization of tracer techniques in the study of agricultural pesticide residues is reviewed under the following headings: lysimeter experiments, micro-ecosystems, translocation in soil, degradation of pesticides in soil, biological availability of soil-applied substances, bound residues in the soil, use of macro- and microautography, double and triple labelling, use of tracer labelling in animal experiments. (U.K.)

  7. Bodily illusions disrupt tactile sensations.

    Science.gov (United States)

    D'Amour, Sarah; Pritchett, Lisa M; Harris, Laurence R

    2015-02-01

    To accurately interpret tactile information, the brain needs to have an accurate representation of the body to which to refer the sensations. Despite this, body representation has only recently been incorporated into the study of tactile perception. Here, we investigate whether distortions of body representation affect tactile sensations. We perceptually altered the length of the arm and the width of the waist using a tendon vibration illusion and measured spatial acuity and sensitivity. Surprisingly, we found reduction in both tactile acuity and sensitivity thresholds when the arm or waist was perceptually altered, which indicates a general disruption of low-level tactile processing. We postulate that the disruptive changes correspond to the preliminary stage as the body representation starts to change and may give new insights into sensory processing in people with long-term or sudden abnormal body representation such as are found in eating disorders or following amputation.

  8. Disrupting the habit of interviewing

    Directory of Open Access Journals (Sweden)

    Eileen Honan

    2014-06-01

    Full Text Available This paper contributes to the growing domain of ‘post-qualitative’ research and experiments with a new (representational form to move away from traditional and clichéd descriptions of research methods. In this paper, I want to interrogate the category of interview, and the habit of interviewing, to disrupt the clichés, so as to allow thinking of different ways of writing/speaking/representing the interactions between researcher and researched that will breathe new life into qualitative inquiries. I will attempt to flatten and shred, destabilise and disrupt our common-sense ideas about interview, including those held most sacred to the qualitative community, that of anonymity and confidentiality, as well as the privilege of the ‘transcript’ in re-presenting interview data.

  9. Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

    Science.gov (United States)

    Sheikh, Ishfaq A; Beg, Mohd A

    2017-12-01

    Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Will Incremental Hemodialysis Preserve Residual Function and Improve Patient Survival?

    Science.gov (United States)

    Davenport, Andrew

    2015-01-01

    The progressive loss of residual renal function in peritoneal dialysis patients is associated with increased mortality. It has been suggested that incremental dialysis may help preserve residual renal function and improve patient survival. Residual renal function depends upon both patient related and dialysis associated factors. Maintaining patients in an over-hydrated state may be associated with better preservation of residual renal function but any benefit comes with a significant risk of cardiovascular consequences. Notably, it is only observational studies that have reported an association between dialysis patient survival and residual renal function; causality has not been established for dialysis patient survival. The tenuous connections between residual renal function and outcomes and between incremental hemodialysis and residual renal function should temper our enthusiasm for interventions in this area. PMID:25385441

  11. Disruptive technologies in higher education

    Directory of Open Access Journals (Sweden)

    Michael Flavin

    2012-08-01

    Full Text Available This paper analyses the role of “disruptive” innovative technologies in higher education. In this country and elsewhere, Higher Education Institutions (HEIs have invested significant sums in learning technologies, with Virtual Learning Environments (VLEs being more or less universal, but these technologies have not been universally adopted and used by students and staff. Instead, other technologies not owned or controlled by HEIs are widely used to support learning and teaching. According to Christensen's theory of Disruptive Innovation, these disruptive technologies are not designed explicitly to support learning and teaching in higher education, but have educational potential. This study uses Activity Theory and Expansive Learning to analyse data regarding the impact of disruptive technologies. The data were obtained through a questionnaire survey about awareness and use of technologies, and through observation and interviews, exploring participants’ actual practice. The survey answers tended to endorse Disruptive Innovation theory, with participants establishing meanings for technologies through their use of them, rather than in keeping with a designer's intentions. Observation revealed that learners use a narrow range of technologies to support learning, but with a tendency to use resources other than those supplied by their HEIs. Interviews showed that participants use simple and convenient technologies to support their learning and teaching. This study identifies a contradiction between learning technologies made available by HEIs, and technologies used in practice. There is no evidence to suggest that a wide range of technologies is being used to support learning and teaching. Instead, a small range of technologies is being used for a wide range of tasks. Students and lecturers are not dependent on their HEIs to support learning and teaching. Instead, they self-select technologies, with use weighted towards established brands. The

  12. Engineering analysis of TFTR disruption

    International Nuclear Information System (INIS)

    Murray, J.G.; Rothe, K.E.; Bronner, G.

    1984-09-01

    This report covers an engineering approach quantifying the currents, forces, and times, as well as plasma position, for the worst-case disruption based on engineerign circuit assumptions for the plasma. As the plasma moves toward the wall during the current-decay phase of disruption, the wall currents affect the rate of movement and, hence, the decay time. The calculated structure-induced currents differ considerably from those calculated using a presently available criterion, which specifies that the plasma remains stationary in the center of the torus while decaying in 10 ms. This report outlines the method and basis for the engineering calculation used to determine the current and forces as a function of the circuit characteristics. It provides specific calculations for the Tokamak Fusion Test Reactor (TFTR) with variations in parameters such as the thermal decay time, the torus resistance, and plasma temperature during the current decay. The study reviews possible ways to reduce the disruption damage of TFTR by reducing the magnitude of the plasma external field energy that is absorbed by the plasma during the current decay

  13. Engineering analysis of TFTR disruption

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J.G.; Rothe, K.E.; Bronner, G.

    1984-09-01

    This report covers an engineering approach quantifying the currents, forces, and times, as well as plasma position, for the worst-case disruption based on engineerign circuit assumptions for the plasma. As the plasma moves toward the wall during the current-decay phase of disruption, the wall currents affect the rate of movement and, hence, the decay time. The calculated structure-induced currents differ considerably from those calculated using a presently available criterion, which specifies that the plasma remains stationary in the center of the torus while decaying in 10 ms. This report outlines the method and basis for the engineering calculation used to determine the current and forces as a function of the circuit characteristics. It provides specific calculations for the Tokamak Fusion Test Reactor (TFTR) with variations in parameters such as the thermal decay time, the torus resistance, and plasma temperature during the current decay. The study reviews possible ways to reduce the disruption damage of TFTR by reducing the magnitude of the plasma external field energy that is absorbed by the plasma during the current decay.

  14. Measurement of perceived disruption during rebuilding following Hurricane Andrew.

    Science.gov (United States)

    Burnett, K; Ironson, G; Benight, C; Wynings, C; Greenwood, D; Carver, C S; Cruess, D; Baum, A; Schneiderman, N

    1997-10-01

    The purpose of this study was to develop and evaluate a measure of perceived disruption during rebuilding following a disaster. Two eight-item scales, which measured intensity of disruption during the entire repair phase (Intensity-RP) and intensity of disruption during the past month (Intensity-PM) were developed and administered to 135 survivors of Hurricane Andrew. At 9 to 12 months postdisaster, Intensity-RP and Intensity-PM were both significantly associated with scores on the Global Severity Index of the SCL-90-R, and with scores on the Impact of Event-Intrusion Scale; Intensity-PM alone was significantly associated with PTSD scores. Regression analyses indicated that each scale contributed significant unique variance in predicting mental health symptoms, even after controlling for relevant demographic and initial disaster exposure variables.

  15. Marital Disruption and Allostatic Load in Late Life.

    Science.gov (United States)

    Rote, Sunshine

    2017-06-01

    This study examines the link between marital disruption and biological risk, and asks whether the association of this precarious life event with health is contingent on marital loss duration and history. Data are drawn from the National Social Life, Health, and Aging Project ( N = 1,414), and Poisson regressions are presented for allostatic load and logistic regressions for individual biomarkers. The currently unmarried with more distant marital disruptions exhibit higher levels of allostatic load than the currently married, which is primarily driven by dysregulation of cardiovascular and metabolic indicators. Results also reveal the differing ways marital disruption "gets under the skin" with widowhood associated with compromised inflammatory, metabolic, and cardiovascular functioning, and divorce with cardiovascular and neuroendocrine markers. Findings lend support for both the crisis and chronic strain models, and likely reflect normative expectations of the timing of life events, decrements in marital resources, and selection processes.

  16. Disruptive innovation as an entrepreneurial process

    NARCIS (Netherlands)

    Chandra, Y.; Yang, S.-J.S.; Singh, P.; Prajogo, D.; O'Neill, P.; Rahman, S.

    2008-01-01

    Research on conditions and causal mechanisms that influence disruptive innovation has been relatively unexplored in the extant research in disruptive innovation. By re-conceptualizing disruptive innovation as an entrepreneurial process at product, firm and industry levels, this paper draws on

  17. Revision Hope: Writing Disruption in Composition Studies.

    Science.gov (United States)

    Jung, Julie

    1997-01-01

    Uses Roland Barthes's metaphor of the "punctum" to explore the transformative potential of disruptions. Argues that writing teachers have been trained to read disruption in texts and classrooms as "evidence of poor taste or failed pedagogy," but that disruptions delay closure and thereby create spaces wherein theories and…

  18. Disruption and Distinctiveness in Higher Education

    Science.gov (United States)

    Purcell, Wendy

    2014-01-01

    "Disruption"--while an evocative word triggering feelings of anxiety and perhaps even fear--also signals renewal and growth. The Higher Education (HE) sector in England has experienced some profound disruption over the years, and yet has emerged stronger and renewed in many ways. The impact of recent disruptive forces, from fees to the…

  19. Routine Responses to Disruption of Routines

    Science.gov (United States)

    Guha, Mahua

    2015-01-01

    "Organisational routines" is a widely studied research area. However, there is a dearth of research on disruption of routines. The few studies on disruption of routines discussed problem-solving activities that are carried out in response to disruption. In contrast, this study develops a theory of "solution routines" that are a…

  20. Global dual-sourcing strategy: is it effective in mitigating supply disruption?

    OpenAIRE

    Ahmad Mustaffa, Nurakmal

    2015-01-01

    Most firms are still failing to think strategically and systematically about managing supply disruption risk and most of the supply chain management efforts are focused on reducing supply chain operation costs rather than managing disruption. Some innovative firms have taken steps to implement supply chain risk management (SCRM). Inventory management is part of SCRM because supply disruptions negatively affect the reliability of deliveries from suppliers and the costs associate...

  1. Disruption of thyroxine and sex hormones by 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH) in American kestrels (Falco sparverius) and associations with reproductive and behavioral changes.

    Science.gov (United States)

    Marteinson, Sarah C; Palace, Vince; Letcher, Robert J; Fernie, Kim J

    2017-04-01

    1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH - formerly TBECH) is an emerging brominated flame retardant (BFR) pollutant with androgen potentiating ability and other endocrine disrupting effects in birds and fish. The objectives of this study were to determine the effects of exposure to environmentally-relevant levels of DBE-DBCH on circulating levels of thyroid and sex steroid hormones in American kestrels, and if hormonal concentrations were related to previously reported changes in reproductive success and courtship behaviors. Sixteen kestrel pairs were exposed to 0.239ng β-DBE-DBCH/g kestrel/day by diet, based on concentrations in wild bird eggs, from 4 weeks before pairing until the chicks hatched (mean 82 d), and were compared with vehicle-only-exposed control pairs (n=15). As previously reported, DBE-DBCH concentrations were not detected in tissue or eggs of these birds, nor were any potential metabolites, despite the low method limits of detection (≤0.4ng/g wet weight), suggesting it may be rapidly metabolized and/or eliminated by the kestrels. Nevertheless, exposed kestrels demonstrated changes in reproduction and behavior, indicating an effect from exposure. During early breeding, males were sampled at multiple time points at pairing and during courtship and incubation; females were blood sampled at pairing only; both sexes were sampled at the end of the season. All comparisons are made to control males or control females, and the relative differences in hormone concentrations between treatment and control birds, calculated separately for each sex, are presented for each time point. Males exposed to β-DBE-DBCH demonstrated significantly (p=0.05) lower concentrations of total thyroxine (TT 4 ) overall, that were 11-28% lower than those of control males at the individual sampling points, yet significantly higher (p=0.03) concentrations of free thyroxine (FT 4 ), that were 5-13% higher than those of control males at the individual sampling

  2. The evolution of substrate specificity-associated residues and Ca(2+) -binding motifs in EF-hand-containing type II NAD(P)H dehydrogenases.

    Science.gov (United States)

    Hao, Meng-Shu; Rasmusson, Allan G

    2016-07-01

    Most eukaryotic organisms, except some animal clades, have mitochondrial alternative electron transport enzymes that allow respiration to bypass the energy coupling in oxidative phosphorylation. The energy bypass enzymes in plants include the external type II NAD(P)H dehydrogenases (DHs) of the NDB family, which are characterized by an EF-hand domain for Ca(2+) binding. Here we investigate these plant enzymes by combining molecular modeling with evolutionary analysis. Molecular modeling of the Arabidopsis thaliana AtNDB1 with the yeast ScNDI1 as template revealed distinct similarities in the core catalytic parts, and highlighted the interaction between the pyridine nucleotide and residues correlating with NAD(P)H substrate specificity. The EF-hand domain of AtNDB1 has no counterpart in ScNDI1, and was instead modeled with Ca(2+) -binding signal transducer proteins. Combined models displayed a proximity of the AtNDB1 EF-hand domain to the substrate entrance side of the catalytic part. Evolutionary analysis of the eukaryotic NDB-type proteins revealed ancient and recent reversions between the motif observed in proteins specific for NADH (acidic type) and NADPH (non-acidic type), and that the clade of enzymes with acidic motifs in angiosperms derives from non-acidic-motif NDB-type proteins present in basal plants, fungi and protists. The results suggest that Ca(2+) -dependent external NADPH oxidation is an ancient process, indicating that it has a fundamental importance for eukaryotic cellular redox metabolism. In contrast, the external NADH DHs in plants are products of a recent expansion, mirroring the expansion of the alternative oxidase family. © 2016 Scandinavian Plant Physiology Society.

  3. [Residual neuromuscular blockade].

    Science.gov (United States)

    Fuchs-Buder, T; Schmartz, D

    2017-06-01

    Even small degrees of residual neuromuscular blockade, i. e. a train-of-four (TOF) ratio >0.6, may lead to clinically relevant consequences for the patient. Especially upper airway integrity and the ability to swallow may still be markedly impaired. Moreover, increasing evidence suggests that residual neuromuscular blockade may affect postoperative outcome of patients. The incidence of these small degrees of residual blockade is relatively high and may persist for more than 90 min after a single intubating dose of an intermediately acting neuromuscular blocking agent, such as rocuronium and atracurium. Both neuromuscular monitoring and pharmacological reversal are key elements for the prevention of postoperative residual blockade.

  4. TENORM: Wastewater Treatment Residuals

    Science.gov (United States)

    Water and wastes which have been discharged into municipal sewers are treated at wastewater treatment plants. These may contain trace amounts of both man-made and naturally occurring radionuclides which can accumulate in the treatment plant and residuals.

  5. Smog induces oxidative stress and microbiota disruption

    Directory of Open Access Journals (Sweden)

    Tit-Yee Wong

    2017-04-01

    Full Text Available Smog is created through the interactions between pollutants in the air, fog, and sunlight. Air pollutants, such as carbon monoxide, heavy metals, nitrogen oxides, ozone, sulfur dioxide, volatile organic vapors, and particulate matters, can induce oxidative stress in human directly or indirectly through the formation of reactive oxygen species. The outermost boundary of human skin and mucous layers are covered by a complex network of human-associated microbes. The relation between these microbial communities and their human host are mostly mutualistic. These microbes not only provide nutrients, vitamins, and protection against other pathogens, they also influence human's physical, immunological, nutritional, and mental developments. Elements in smog can induce oxidative stress to these microbes, leading to community collapse. Disruption of these mutualistic microbiota may introduce unexpected health risks, especially among the newborns and young children. Besides reducing the burning of fossil fuels as the ultimate solution of smog formation, advanced methods by using various physical, chemical, and biological means to reduce sulfur and nitrogen contains in fossil fuels could lower smog formation. Additionally, information on microbiota disruption, based on functional genomics, culturomics, and general ecological principles, should be included in the risk assessment of prolonged smog exposure to the health of human populations.

  6. Smog induces oxidative stress and microbiota disruption.

    Science.gov (United States)

    Wong, Tit-Yee

    2017-04-01

    Smog is created through the interactions between pollutants in the air, fog, and sunlight. Air pollutants, such as carbon monoxide, heavy metals, nitrogen oxides, ozone, sulfur dioxide, volatile organic vapors, and particulate matters, can induce oxidative stress in human directly or indirectly through the formation of reactive oxygen species. The outermost boundary of human skin and mucous layers are covered by a complex network of human-associated microbes. The relation between these microbial communities and their human host are mostly mutualistic. These microbes not only provide nutrients, vitamins, and protection against other pathogens, they also influence human's physical, immunological, nutritional, and mental developments. Elements in smog can induce oxidative stress to these microbes, leading to community collapse. Disruption of these mutualistic microbiota may introduce unexpected health risks, especially among the newborns and young children. Besides reducing the burning of fossil fuels as the ultimate solution of smog formation, advanced methods by using various physical, chemical, and biological means to reduce sulfur and nitrogen contains in fossil fuels could lower smog formation. Additionally, information on microbiota disruption, based on functional genomics, culturomics, and general ecological principles, should be included in the risk assessment of prolonged smog exposure to the health of human populations. Copyright © 2017. Published by Elsevier B.V.

  7. Disruptive behaviour in the perioperative setting: a contemporary review.

    Science.gov (United States)

    Villafranca, Alexander; Hamlin, Colin; Enns, Stephanie; Jacobsohn, Eric

    2017-02-01

    enforced, regular performance feedback, and clinician coaching/remediation as required. Disruptive behaviour remains a part of operating room culture, with many associated deleterious effects. There is a widely accepted view that disruptive behaviour can lead to increased patient morbidity and mortality. This is mechanistically plausible, but more rigorous studies are required to confirm the effects and estimate their magnitude. An important measure that individual clinicians can take is to monitor and control their own behaviour, including their responses to disruptive behaviour.

  8. Residuation in orthomodular lattices

    Directory of Open Access Journals (Sweden)

    Chajda Ivan

    2017-04-01

    Full Text Available We show that every idempotent weakly divisible residuated lattice satisfying the double negation law can be transformed into an orthomodular lattice. The converse holds if adjointness is replaced by conditional adjointness. Moreover, we show that every positive right residuated lattice satisfying the double negation law and two further simple identities can be converted into an orthomodular lattice. In this case, also the converse statement is true and the corresponence is nearly one-to-one.

  9. Changing perspectives in medical practice: disruptive innovation.

    Science.gov (United States)

    Paterick, Zachary R; Pradhan, Sala R; Paterick, Timothy E; Waterhouse, Blake E

    2009-01-01

    Disruptive innovation represents a business model that identifies a market location and increases consumer options. Retail clinics may represent a disruptive healthcare innovation that identifies strategies to reduce the cost of healthcare at the primary care level. The future of healthcare demands disruptive innovation that will allow for the 50 million uninsured members of our society to receive medical care. Disruptive innovative solutions need to ensure access, quality, and reasonable cost. Retail clinics represent the tip of the iceberg in disruptive innovative thinking. The obstacles that retail clinics must solve will be lessons learned for those that identify future innovative techniques.

  10. Characterization of Hospital Residuals

    International Nuclear Information System (INIS)

    Blanco Meza, A.; Bonilla Jimenez, S.

    1997-01-01

    The main objective of this investigation is the characterization of the solid residuals. A description of the handling of the liquid and gassy waste generated in hospitals is also given, identifying the source where they originate. To achieve the proposed objective the work was divided in three stages: The first one was the planning and the coordination with each hospital center, in this way, to determine the schedule of gathering of the waste can be possible. In the second stage a fieldwork was made; it consisted in gathering the quantitative and qualitative information of the general state of the handling of residuals. In the third and last stage, the information previously obtained was organized to express the results as the production rate per day by bed, generation of solid residuals for sampled services, type of solid residuals and density of the same ones. With the obtained results, approaches are settled down to either determine design parameters for final disposition whether for incineration, trituration, sanitary filler or recycling of some materials, and storage politics of the solid residuals that allow to determine the gathering frequency. The study concludes that it is necessary to improve the conditions of the residuals handling in some aspects, to provide the cleaning personnel of the equipment for gathering disposition and of security, minimum to carry out this work efficiently, and to maintain a control of all the dangerous waste, like sharp or polluted materials. In this way, an appreciable reduction is guaranteed in the impact on the atmosphere. (Author) [es

  11. Risk factors for wound disruption following cesarean delivery.

    Science.gov (United States)

    Subramaniam, Akila; Jauk, Victoria C; Figueroa, Dana; Biggio, Joseph R; Owen, John; Tita, Alan T N

    2014-08-01

    Risk factors for post-cesarean wound infection, but not disruption, are well-described in the literature. The primary objective of this study was to identify risk factors for non-infectious post-cesarean wound disruption. Secondary analysis was conducted using data from a single-center randomized controlled trial of staple versus suture skin closure in women ≥24 weeks' gestation undergoing cesarean delivery. Wound disruption was defined as subcutaneous skin or fascial dehiscence excluding primary wound infections. Composite wound morbidity (disruption or infection) was examined as a secondary outcome. Patient demographics, medical co-morbidities, and intrapartum characteristics were evaluated as potential risk factors using multivariable logistic regression. Of the 398 randomized patients, 340, including 26 with disruptions (7.6%) met inclusion criteria and were analyzed. After multivariable adjustments, African-American race (aOR 3.9, 95% CI 1.1-13.8) and staple - as opposed to suture - wound closure (aOR 5.4, 95% CI 1.8-16.1) remained significant risk factors for disruption; non-significant increases were observed for body mass index ≥30 (aOR 2.1, 95% CI 0.6-7.5), but not for diabetes mellitus (aOR 0.9, 95% CI 0.3-2.9). RESULTS for composite wound morbidity were similar. Skin closure with staples, African-American race, and considering the relatively small sample size, potentially obesity are associated with increased risk of non-infectious post-cesarean wound disruption.

  12. Parental Divorce, Life-Course Disruption, and Adult Depression.

    Science.gov (United States)

    Ross, Catherine E.; Mirowsky, John

    1999-01-01

    Reports on a national sample of adults (N=2,592) surveyed on the association between adult depression and childhood parental divorce. Results suggest that parental divorce may disrupt a person's life course and create lifelong consequences for their well being, by lowering socioeconomic status and increasing problems in interpersonal…

  13. Metabolic effects of bariatric surgery in mouse models of circadian disruption.

    Science.gov (United States)

    Arble, D M; Sandoval, D A; Turek, F W; Woods, S C; Seeley, R J

    2015-08-01

    Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity. Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption. VSG led to a reduction in body weight and fat mass in both Clock(Δ19) mutant and constant-light mouse models (Pdisruption. Interestingly, the decrease in body weight occurred without altering diurnal feeding or activity patterns (P>0.05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (Pdisruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, as the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption.

  14. A data bank of disruptive discharges in ASDEX

    International Nuclear Information System (INIS)

    Ludescher, C.; Lackner, K.; Schneider, F.

    1994-03-01

    The compilation of data banks relating to plasma disruptions is important for the design of next-step devices and tokamak reactors, as a means of establishing safe operation regimes and assessing the residual risk from such events. ASDEX has an operational history of 33509 plasma shots covering an exceptionally wide range of machine conditions: Divertor/limiter configurations; Ohmic, NBI, ICRH and LH heating; carbonization, boronization wall-conditioning, gas-puff and pellet refuelling. We have compiled a data base of the Disruptive Operationl Regimes in ASDEX (DORA), which contains the relevant information for all ASDEX-discharges and is available on tape and readable by different data bank systems for further evaluation. We first describe the criteria applied to recognize and classify disruptions and the information about them stored in the file. In a second part we use the DORA file for some sample applications of physical or engineering interest. In an appendix we give the data and format information necessary to read the DORA file. (orig.)

  15. Development of multi-residue method for the determination of pesticides in cereal matrices by isotopic dilution associated to liquid chromatography coupled to tandem mass spectrometry after pressurized liquid extraction

    International Nuclear Information System (INIS)

    El Mrabet, Khadija

    2008-01-01

    Pesticides are nowadays considered as toxic for human health. The maximal residues levels authorized in water and foodstuff are more and more strict. Therefore, selective analytical techniques are necessary for their identification and their quantification. The aim of this thesis was to develop a multi-residue method for the determination of pesticides by isotopic dilution associated to liquid chromatography (LC) coupled with tandem mass spectrometry (MS 2 ) after pressurized liquid extraction. In a first step, an analysis method of phenyl-ureas and triazines in groundwater by isotopic dilution associated to LC/MS 2 after solid phase extraction has been developed. The method has been validated and evaluated by participating to an inter-laboratory study. Concerning cereals, an extraction method of pesticides associated to an analysis by LC/MS 2 has been developed for thirty-eight pesticides representative of twenty-six chemicals families and fourteen labeled compounds in wheat. The analysis has been carried out in reversed phase chromatography. Separation and detection conditions have been optimized. A global analytical protocol consisting of a pressurized liquid extraction step using acetonitrile at 100 deg. C and at 100 bars and followed by purification step of the resulting extract on a polymeric sorbent was developed. The developed method enables to extract thirty-eight pesticides and fourteen labeled compounds from wheat with recovery yield about 85% (RSD =4%, n=3). Moreover, the results show that the application of isotopic dilution can be complex. Although some improvements need to be added regarding experimentation of aged matrices or contaminated samples, the potential of the method has been demonstrated. (author) [fr

  16. Disruptive Innovation in Numerical Hydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Waltz, Jacob I. [Los Alamos National Laboratory

    2012-09-06

    We propose the research and development of a high-fidelity hydrodynamic algorithm for tetrahedral meshes that will lead to a disruptive innovation in the numerical modeling of Laboratory problems. Our proposed innovation has the potential to reduce turnaround time by orders of magnitude relative to Advanced Simulation and Computing (ASC) codes; reduce simulation setup costs by millions of dollars per year; and effectively leverage Graphics Processing Unit (GPU) and future Exascale computing hardware. If successful, this work will lead to a dramatic leap forward in the Laboratory's quest for a predictive simulation capability.

  17. Incumbent response to disruptive innovation

    DEFF Research Database (Denmark)

    Kaulio, Matti; Thorén, Kent; Rohrbeck, René

    changes, however successful in minor business model adaptions. An implication hereof is that the business model concept as such has low predictive power in explaining success and failure and is in the need of an operationalization. In addition, the article discusses the relationship between technological...... in relation to disruptive change. In relation to technical change the case company has successfully in transferred its technology from one generation to the next during more than 20 years. In relation to business model change the case company has been proactive but not successful in major business model...... innovation and business innovation....

  18. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage

    2014-01-01

    implied porcine RFI is regulated by multiple biological mechanisms, although the metabolic processes might be the most important. Olfactory transduction pathway controlling the perception of feed via smell, insulin pathway controlling food intake might be important pathways for RFI. Furthermore, our study....... Metabolic pathway was significantly associated with both RFIs. Other biological pathways regulating phagosome, tight junctions, olfactory transduction, and insulin secretion were significantly associated with both RFI traits when relaxed threshold for cut-off p-value was used (p ≤ 0.05). These results...

  19. TMS produces two dissociable types of speech disruption.

    Science.gov (United States)

    Stewart, L; Walsh, V; Frith, U; Rothwell, J C

    2001-03-01

    We aimed to use repetitive transcranial magnetic stimulation (rTMS) to disrupt speech with the specific objective of dissociating speech disruption according to whether or not it was associated with activation of the mentalis muscle. Repetitive transcranial magnetic stimulation (rTMS) was applied over two sites of the right and left hemisphere while subjects counted aloud and recited the days of the week, months of the year, and nursery rhymes. Analysis of EMG data and videotaped recordings showed that rTMS applied over a posterior site, lateral to the motor hand area of both the right and the left hemisphere resulted in speech disruption that was accompanied by activation of the mentalis muscle, while rTMS applied over an anterior site on the left but not the right hemisphere resulted in speech disruption that was dissociated from activation of the mentalis muscle. The findings provide a basis for the use of subthreshold stimulation over the extrarolandic speech disruption site in order to probe the functional properties of this area and to test psychological theories of linguistic function. Copyright 2001 Academic Press.

  20. Pesticide residues in birds and mammals

    Science.gov (United States)

    Stickel, L.F.; Edwards, C.A.

    1973-01-01

    exposure to an organochlorine pesticide, the concentrations of residues in the different tissues are ordinarily directly correlated with each other. When the dosage is at lethal levels, or when stored residues are mobilised to lethal levels, the balanced relationship is disrupted. The concentrations of residues in the brain provide the most rigorous criteria for diagnosis of death due to these chemicals, and levels are generally similar across a wide range of species of birds and mammals. Residues in liver are closely correlated with recent dose, either from direct intake or from mobilisation from storage, and so reflect hazardous exposure. Residues in the whole carcass show the storage reserve, and so indicate the potential for adverse effects from lethal mobilisation or from the continuous slow mobilisation that occurs during the normal processes of metabolism and excretion. A synchronous, rapid, and widespread decline in weight and thickness of shells of eggs laid by many species of wild birds occurred in the late 1940's and has persisted. Birds of prey were primarily affected; exceptions apparently are the result of lesser exposure because of different food habits. Many species of fish-eating birds are also affected. Others, however, appear to be more resistant and to accumulate much higher residues before shell-thinning occurs. Seed-eating birds do not appear to have been generally affected; their exposure is ordinarily lower, but physiological factors also seem to be involved. A relationship between shell-thinning and population decline has been established for many species. In exceptional cases, such as the herring gull, persistent re-nesting and other population reactions have overcome adverse effects at the population level. The discovery of shell-thinning among natural populations, and the hypothesis that this thinning was related to the occurrence of organochlorine pesticides, stimulated experimental studies to determine wheth

  1. Disruptive innovation for social change.

    Science.gov (United States)

    Christensen, Clayton M; Baumann, Heiner; Ruggles, Rudy; Sadtler, Thomas M

    2006-12-01

    Countries, organizations, and individuals around the globe spend aggressively to solve social problems, but these efforts often fail to deliver. Misdirected investment is the primary reason for that failure. Most of the money earmarked for social initiatives goes to organizations that are structured to support specific groups of recipients, often with sophisticated solutions. Such organizations rarely reach the broader populations that could be served by simpler alternatives. There is, however, an effective way to get to those underserved populations. The authors call it "catalytic innovation." Based on Clayton Christensen's disruptive-innovation model, catalytic innovations challenge organizational incumbents by offering simpler, good-enough solutions aimed at underserved groups. Unlike disruptive innovations, though, catalytic innovations are focused on creating social change. Catalytic innovators are defined by five distinct qualities. First, they create social change through scaling and replication. Second, they meet a need that is either overserved (that is, the existing solution is more complex than necessary for many people) or not served at all. Third, the products and services they offer are simpler and cheaper than alternatives, but recipients view them as good enough. Fourth, they bring in resources in ways that initially seem unattractive to incumbents. And fifth, they are often ignored, put down, or even encouraged by existing organizations, which don't see the catalytic innovators' solutions as viable. As the authors show through examples in health care, education, and economic development, both nonprofit and for-profit groups are finding ways to create catalytic innovation that drives social change.

  2. Tokamak disruption heat flux simulator

    International Nuclear Information System (INIS)

    Langhoff, M.; Hess, G.; Gahl, J.; Ingram, R.

    1990-01-01

    A coaxial plasma gun system, operating in the deflagration mode, has been built and fired at the University of New Mexico. This system, powered by a 100 kJ capacitor bank, was designed to give a variable pulse length of approximately 50-100 us. The gun is intended to deliver to a target an energy deposition density of 1 kJ per cm 2 via impact with a deuterium plasma possessing a highly directed energy. This system should simulate on the target, over an area of approximately 10 cm 2 , the heat flux of a tokamak plasma disruption on plasma facing components. Current diagnostics for the system are rather rudimentary but sufficient for determination of plasma pulse characteristics and energy transfer to target. Electrical measurements include bank voltage measured via resistive voltage dividers, and bank current measured via Rogowski coil. The shape of the plasma, its position relative to the target area, and the final impact area, is determined via open-shutter photography and the use of witness plates. Total energy deposited onto targets will be determined through simple calorimetry and careful target mass measurements. Preliminary results describing the ablation of carbon targets exposed to disruption like heat fluxes will be presented as well as a description of the experimental apparatus

  3. Prenatal exposure to endocrine disrupting chemicals and birth weight – a prospective cohort study

    NARCIS (Netherlands)

    de Cock, M.; de Boer, M.R.; Lamoree, M.; Legler, J.; van de Bor, M.

    2016-01-01

    Prenatal exposure to endocrine disrupting chemicals may affect fetal development through disruption of hormonal actions and epigenetic modifications, potentially predisposing individuals to later on-set health risks, such as obesity. The objective of this study was to determine associations between

  4. Disruptions seen arising from nuclear rate shock

    International Nuclear Information System (INIS)

    Utroska, D.

    1984-01-01

    Recent reports by the public utility industry and Price Waterhouse conclude that the rate shock associated with some of the over 40 nuclear plants coming on-line in the next few years could disrupt local economies and change the way certain crisis-state electric companies report their financial dealings. Passing the full cost of a plant along to ratepayers can result in a direct reduction in electricity demand and a corresponding flight of consumers from the region. Another effect may be to eliminate allowance for funds used during construction (AFUDC) as an accounting tool if there is no possibility of recovering costs from ratepayers. One report estimates that the lifetime value of nuclear plant costs will likely exceed lifetime fuel savings by $82 to $266 billion. Rate phase-in could mitigate the shock and make it more equitable. 1 table

  5. Action-specific disruption of perceptual confidence.

    Science.gov (United States)

    Fleming, Stephen M; Maniscalco, Brian; Ko, Yoshiaki; Amendi, Namema; Ro, Tony; Lau, Hakwan

    2015-01-01

    Theoretical models of perception assume that confidence is related to the quality or strength of sensory processing. Counter to this intuitive view, we showed in the present research that the motor system also contributes to judgments of perceptual confidence. In two experiments, we used transcranial magnetic stimulation (TMS) to manipulate response-specific representations in the premotor cortex, selectively disrupting postresponse confidence in visual discrimination judgments. Specifically, stimulation of the motor representation associated with the unchosen response reduced confidence in correct responses, thereby reducing metacognitive capacity without changing visual discrimination performance. Effects of TMS on confidence were observed when stimulation was applied both before and after the response occurred, which suggests that confidence depends on late-stage metacognitive processes. These results place constraints on models of perceptual confidence and metacognition by revealing that action-specific information in the premotor cortex contributes to perceptual confidence. © The Author(s) 2014.

  6. Management of NORM Residues

    International Nuclear Information System (INIS)

    2013-06-01

    The IAEA attaches great importance to the dissemination of information that can assist Member States in the development, implementation, maintenance and continuous improvement of systems, programmes and activities that support the nuclear fuel cycle and nuclear applications, and that address the legacy of past practices and accidents. However, radioactive residues are found not only in nuclear fuel cycle activities, but also in a range of other industrial activities, including: - Mining and milling of metalliferous and non-metallic ores; - Production of non-nuclear fuels, including coal, oil and gas; - Extraction and purification of water (e.g. in the generation of geothermal energy, as drinking and industrial process water; in paper and pulp manufacturing processes); - Production of industrial minerals, including phosphate, clay and building materials; - Use of radionuclides, such as thorium, for properties other than their radioactivity. Naturally occurring radioactive material (NORM) may lead to exposures at some stage of these processes and in the use or reuse of products, residues or wastes. Several IAEA publications address NORM issues with a special focus on some of the more relevant industrial operations. This publication attempts to provide guidance on managing residues arising from different NORM type industries, and on pertinent residue management strategies and technologies, to help Member States gain perspectives on the management of NORM residues

  7. Residual viraemia in HIV-1-infected patients with plasma viral load associated with increased blood levels of soluble immune activation markers

    DEFF Research Database (Denmark)

    Ostrowski, S R; Katzenstein, T L; Pedersen, B K

    2008-01-01

    -count, CD4+HLA-DR+, CD8+HLA-DR+CD38+, CD4+CD45RA-CD45RO+, CD8+CD45RA-CD45RO+, CD4+CD45RA+CD62L+, CD8+CD45RA+CD62L+ T cells, IgG or IgM. In conclusion, RV was associated with increased blood levels of soluble immune activation markers in HAART-treated HIV-1-infected patients. The finding that RV...

  8. Genetic Analysis with the Immunochip Platform in Behçet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci

    Science.gov (United States)

    Montes-Cano, Marco-Antonio; García-Lozano, José-Raúl; Conde-Jaldón, Marta; Ortego-Centeno, Norberto; Castillo, María Jesús; Sánchez-Bursón, Juan; Juliá, María Rosa; Solans, Roser; Blanco, Ricardo; Barnosi-Marín, Ana-Celia; Gómez de la Torre, Ricardo; Fanlo, Patricia; Rodríguez-Carballeira, Mónica; Camps, Teresa; Castañeda, Santos; Alegre-Sancho, Juan-Jose; Martín, Javier; González-Escribano, María Francisca

    2016-01-01

    Behcet's disease (BD) is an immuno-mediated vasculitis in which knowledge of its etiology and genetic basis is limited. To improve the current knowledge, a genetic analysis performed with the Immunochip platform was carried out in a population from Spain. A discovery cohort comprising 278 BD cases and 1,517 unaffected controls were genotyped using the Immunochip platform. The validation step was performed on an independent replication cohort composed of 130 BD cases and 600 additional controls. The strongest association signals were observed in the HLA class I region, being HLA-B*51 the highest peak (overall P = 6.82E-32, OR = 3.82). A step-wise conditional logistic regression with classical alleles identified HLA-B*57 and HLA-A*03 as additional independent markers. The amino acid model that best explained the association, includes the position 97 of the HLA-B molecule and the position 66 of the HLA-A. Among the non-HLA loci, the most significant in the discovery analysis were: IL23R (rs10889664: P = 3.81E-12, OR = 2.00), the JRKL/CNTN5 region (rs2848479: P = 5.00E-08, OR = 1.68) and IL12A (rs1874886: P = 6.67E-08, OR = 1.72), which were confirmed in the validation phase (JRKL/CNTN5 rs2848479: P = 3.29E-10, OR = 1.66; IL12A rs1874886: P = 1.62E-08, OR = 1.61). Our results confirm HLA-B*51 as a primary-association marker in predisposition to BD and suggest additional independent signals within the class I region, specifically in the genes HLA-A and HLA-B. Regarding the non-HLA genes, in addition to IL-23R, previously reported in our population; IL12A, described in other populations, was found to be a BD susceptibility factor also in Spaniards; finally, a new associated locus was found in the JRKL/CNTN5 region. PMID:27548383

  9. Phosphorylation of tyrosine residues 31 and 118 on paxillin regulates cell migration through an association with CRK in NBT-II cells.

    Science.gov (United States)

    Petit, V; Boyer, B; Lentz, D; Turner, C E; Thiery, J P; Vallés, A M

    2000-03-06

    Identification of signaling molecules that regulate cell migration is important for understanding fundamental processes in development and the origin of various pathological conditions. The migration of Nara Bladder Tumor II (NBT-II) cells was used to determine which signaling molecules are specifically involved in the collagen-mediated locomotion. We show here that paxillin is tyrosine phosphorylated after induction of motility on collagen. Overexpression of paxillin mutants in which tyrosine 31 and/or tyrosine 118 were replaced by phenylalanine effectively impaired cell motility. Moreover, stimulation of motility by collagen preferentially enhanced the association of paxillin with the SH2 domain of the adaptor protein CrkII. Mutations in both tyrosine 31 and 118 diminished the phosphotyrosine content of paxillin and prevented the formation of the paxillin-Crk complex, suggesting that this association is necessary for collagen-mediated NBT-II cell migration. Other responses to collagen, such as cell adhesion and spreading, were not affected by these mutations. Overexpression of wild-type paxillin or Crk could bypass the migration-deficient phenotype. Both the SH2 and the SH3 domains of CrkII are shown to play a critical role in this collagen-mediated migration. These results demonstrate the important role of the paxillin-Crk complex in the collagen-induced cell motility.

  10. Residual-stress measurements

    Energy Technology Data Exchange (ETDEWEB)

    Ezeilo, A.N.; Webster, G.A. [Imperial College, London (United Kingdom); Webster, P.J. [Salford Univ. (United Kingdom)

    1997-04-01

    Because neutrons can penetrate distances of up to 50 mm in most engineering materials, this makes them unique for establishing residual-stress distributions non-destructively. D1A is particularly suited for through-surface measurements as it does not suffer from instrumental surface aberrations commonly found on multidetector instruments, while D20 is best for fast internal-strain scanning. Two examples for residual-stress measurements in a shot-peened material, and in a weld are presented to demonstrate the attractive features of both instruments. (author).

  11. Current disruption in toroidal devices

    International Nuclear Information System (INIS)

    1979-07-01

    Attempts at raising the density or the plasma current in a tokamak above certain critical values generally result in termination of the discharge by a disruption. This sudden end of the plasma current and plasma confinement is accompanied by large induced voltages and currents in the outer structures which, in large tokamaks, can only be handled with considerable effort, and which will probably only be tolerable in reactors as rare accidents. Because of its crucial importance for the construction and operation of tokamaks, this phenomenon and its theoretical interpretation were the subject of a three-day symposium organized by the International Atomic Energy Agency and Max-Planck-Institut fuer Plasmaphysik at Garching from February 14 to 16. (orig./HT)

  12. Automatic location of disruption times in JET.

    Science.gov (United States)

    Moreno, R; Vega, J; Murari, A

    2014-11-01

    The loss of stability and confinement in tokamak plasmas can induce critical events known as disruptions. Disruptions produce strong electromagnetic forces and thermal loads which can damage fundamental components of the devices. Determining the disruption time is extremely important for various disruption studies: theoretical models, physics-driven models, or disruption predictors. In JET, during the experimental campaigns with the JET-C (Carbon Fiber Composite) wall, a common criterion to determine the disruption time consisted of locating the time of the thermal quench. However, with the metallic ITER-like wall (JET-ILW), this criterion is usually not valid. Several thermal quenches may occur previous to the current quench but the temperature recovers. Therefore, a new criterion has to be defined. A possibility is to use the start of the current quench as disruption time. This work describes the implementation of an automatic data processing method to estimate the disruption time according to this new definition. This automatic determination allows both reducing human efforts to locate the disruption times and standardizing the estimates (with the benefit of being less vulnerable to human errors).

  13. Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors

    Science.gov (United States)

    Sukhai, Mahadeo A.; Prabha, Swayam; Hurren, Rose; Rutledge, Angela C.; Lee, Anna Y.; Sriskanthadevan, Shrivani; Sun, Hong; Wang, Xiaoming; Skrtic, Marko; Seneviratne, Ayesh; Cusimano, Maria; Jhas, Bozhena; Gronda, Marcela; MacLean, Neil; Cho, Eunice E.; Spagnuolo, Paul A.; Sharmeen, Sumaiya; Gebbia, Marinella; Urbanus, Malene; Eppert, Kolja; Dissanayake, Dilan; Jonet, Alexia; Dassonville-Klimpt, Alexandra; Li, Xiaoming; Datti, Alessandro; Ohashi, Pamela S.; Wrana, Jeff; Rogers, Ian; Sonnet, Pascal; Ellis, William Y.; Corey, Seth J.; Eaves, Connie; Minden, Mark D.; Wang, Jean C.Y.; Dick, John E.; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D.

    2012-01-01

    Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML. PMID:23202731

  14. Current disruptions in the near-earth neutral sheet region

    International Nuclear Information System (INIS)

    Liu, A.T.Y.; Anderson, B.J.; Takahashi, K.; Zanetti, L.J.; McEntire, R.W.; Potemra, T.A.; Lopez, R.E.; Klumpar, D.M.; Greene, E.M.; Strangeway, R.

    1992-01-01

    Observations from the Charge Composition Explorer in 1985 and 1986 revealed fifteen current disruption events in which the magnetic field fluctuations were large and their onsets coincided well with ground onsets of substorm expansion or intensification. Over the disruption interval, the local magnetic field can change by as much as a factor of ∼7. In general, the stronger the current buildup and the closer the neutral sheet, the larger the resultant field change. There is also a tendency for a larger subsequent enhancement in the AE index with a stronger current buildup prior to current disruption. For events with good pitch angle coverage and extended observation in the neutral sheet region the authors find that the particle pressure increases toward the disruption onset and decreases afterward. Just prior to disruption, either the total particle pressure is isotropic, or the perpendicular component (P perpendicular ) dominates the parallel component (P parallel ), the plasma beta is seen to be as high as ∼70, and the observed plasma pressure gradient at the neutral sheet is large along the tail axis. The deduced local current density associated with pressure gradient is ∼27-80 n/Am 2 and is ∼85-105 mA/m when integrated over the sheet thickness. They infer from these results that just prior to the onset of current disruption, (1) an extremely thin current sheet requiring P parallel > P perpendicular for stress balance does not develop at these distances, (2) the thermal ion orbits are in the chaotic or Speiser regime while the thermal electrons are in the adiabatic regime and, in one case, exhibit peaked fluxes perpendicular to the magnetic field, thus implying no electron orbit chaotization to possibly initiate ion tearing instability, and (3) the neutral sheet is in the unstable regime specified by the cross-field current instability

  15. Composition of carbonization residues

    Energy Technology Data Exchange (ETDEWEB)

    Hupfer; Leonhardt

    1943-11-27

    This report compared the composition of samples from Wesseling and Leuna. In each case the sample was a residue from carbonization of the residues from hydrogenation of the brown coal processed at the plant. The composition was given in terms of volatile components, fixed carbon, ash, water, carbon, hydrogen, oxygen, nitrogen, volatile sulfur, and total sulfur. The result of carbonization was given in terms of (ash and) coke, tar, water, gas and losses, and bitumen. The composition of the ash was given in terms of silicon dioxide, ferric oxide, aluminum oxide, calcium oxide, magnesium oxide, potassium and sodium oxides, sulfur trioxide, phosphorus pentoxide, chlorine, and titanium oxide. The most important difference between the properties of the two samples was that the residue from Wesseling only contained 4% oil, whereas that from Leuna had about 26% oil. Taking into account the total amount of residue processed yearly, the report noted that better carbonization at Leuna could save 20,000 metric tons/year of oil. Some other comparisons of data included about 33% volatiles at Leuna vs. about 22% at Wesseling, about 5 1/2% sulfur at Leuna vs. about 6 1/2% at Leuna, but about 57% ash for both. Composition of the ash differed quite a bit between the two. 1 table.

  16. Designing with residual materials

    NARCIS (Netherlands)

    Walhout, W.; Wever, R.; Blom, E.; Addink-Dölle, L.; Tempelman, E.

    2013-01-01

    Many entrepreneurial businesses have attempted to create value based on the residual material streams of third parties. Based on ‘waste’ materials they designed products, around which they built their company. Such activities have the potential to yield sustainable products. Many of such companies

  17. Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal- and glyoxal-glycated cysteine, arginine, and lysine residues.

    Science.gov (United States)

    Richarme, Gilbert; Mihoub, Mouadh; Dairou, Julien; Bui, Linh Chi; Leger, Thibaut; Lamouri, Aazdine

    2015-01-16

    Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we show that human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate, respectively. DJ-1 deglycates cysteines, arginines, and lysines (the three major glycated amino acids) of serum albumin, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and aspartate aminotransferase and thus reactivates these proteins. DJ-1 prevented protein glycation in an Escherichia coli mutant deficient in the DJ-1 homolog YajL and restored cell viability in glucose-containing media. These results suggest that DJ-1-associated Parkinsonism results from excessive protein glycation and establishes DJ-1 as a major anti-glycation and anti-aging protein. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Hole traps associated with high-concentration residual carriers in p-type GaAsN grown by chemical beam epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Elleuch, Omar, E-mail: mr.omar.elleuch@gmail.com; Wang, Li; Lee, Kan-Hua; Demizu, Koshiro; Ikeda, Kazuma; Kojima, Nobuaki; Ohshita, Yoshio; Yamaguchi, Masafumi [Toyota Technological Institute, 2-12-1 Hisakata, Tempaku, Nagoya 468-8511 (Japan)

    2015-01-28

    The hole traps associated with high background doping in p-type GaAsN grown by chemical beam epitaxy are studied based on the changes of carrier concentration, junction capacitance, and hole traps properties due to the annealing. The carrier concentration was increased dramatically with annealing time, based on capacitance–voltage (C–V) measurement. In addition, the temperature dependence of the junction capacitance (C–T) was increased rapidly two times. Such behavior is explained by the thermal ionization of two acceptor states. These acceptors are the main cause of high background doping in the film, since the estimated carrier concentration from C–T results explains the measured carrier concentration at room temperature using C–V method. The acceptor states became shallower after annealing, and hence their structures are thermally unstable. Deep level transient spectroscopy (DLTS) showed that the HC2 hole trap was composed of two signals, labeled HC21 and HC22. These defects correspond to the acceptor levels, as their energy levels obtained from DLTS are similar to those deduced from C–T. The capture cross sections of HC21 and HC22 are larger than those of single acceptors. In addition, their energy levels and capture cross sections change in the same way due to the annealing. This tendency suggests that HC21 and HC22 signals originate from the same defect which acts as a double acceptor.

  19. Hole traps associated with high-concentration residual carriers in p-type GaAsN grown by chemical beam epitaxy

    International Nuclear Information System (INIS)

    Elleuch, Omar; Wang, Li; Lee, Kan-Hua; Demizu, Koshiro; Ikeda, Kazuma; Kojima, Nobuaki; Ohshita, Yoshio; Yamaguchi, Masafumi

    2015-01-01

    The hole traps associated with high background doping in p-type GaAsN grown by chemical beam epitaxy are studied based on the changes of carrier concentration, junction capacitance, and hole traps properties due to the annealing. The carrier concentration was increased dramatically with annealing time, based on capacitance–voltage (C–V) measurement. In addition, the temperature dependence of the junction capacitance (C–T) was increased rapidly two times. Such behavior is explained by the thermal ionization of two acceptor states. These acceptors are the main cause of high background doping in the film, since the estimated carrier concentration from C–T results explains the measured carrier concentration at room temperature using C–V method. The acceptor states became shallower after annealing, and hence their structures are thermally unstable. Deep level transient spectroscopy (DLTS) showed that the HC2 hole trap was composed of two signals, labeled HC21 and HC22. These defects correspond to the acceptor levels, as their energy levels obtained from DLTS are similar to those deduced from C–T. The capture cross sections of HC21 and HC22 are larger than those of single acceptors. In addition, their energy levels and capture cross sections change in the same way due to the annealing. This tendency suggests that HC21 and HC22 signals originate from the same defect which acts as a double acceptor

  20. Oncogenomic disruptions in arsenic-induced carcinogenesis.

    Science.gov (United States)

    Sage, Adam P; Minatel, Brenda C; Ng, Kevin W; Stewart, Greg L; Dummer, Trevor J B; Lam, Wan L; Martinez, Victor D

    2017-04-11

    Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process.

  1. Validation of welded joint residual stress simulation

    International Nuclear Information System (INIS)

    Computational mechanics is being increasingly applied to predict the state of residual stress in welded joints for nuclear power plant applications. Motives for undertaking such calculations include optimising the design of welded joints and weld procedures, assessing the effectiveness of mitigation processes, providing more realistic inputs to structural integrity assessments and underwriting safety cases for operating nuclear power plant. Fusion welding processes involve intense localised heating to melt the surfaces to be joined and introduction of molten weld filler metal. A complex residual stress field develops at the weld through solidification, differential thermal contraction, cyclic thermal plasticity, phase transformation and chemical diffusion processes. The calculation of weld residual stress involves detailed non-linear analyses where many assumptions and approximations have to be made. In consequence, the accuracy and reliability of solutions can be highly variable. This paper illustrates the degree of variability that can arise in weld residual stress simulation results and summarises the new R6 guidelines which aim to improve the reliability and accuracy of computational predictions. The requirements for validating weld simulations are reviewed where residual stresses are to be used in fracture mechanics analysis. This includes a discussion of how to obtain and interpret measurements from mock-ups, benchmark weldments and published data. Benchmark weldments are described that illustrate some of the issues and show how validation of numerical prediction of weld residual stress can be achieved. Finally, plans for developing the weld modelling guidelines and associated benchmarks are outlined

  2. Survey of disruption causes at JET

    NARCIS (Netherlands)

    de Vries, P. C.; Johnson, M. F.; Alper, B.; Buratti, P.; Hender, T. C.; Koslowski, H. R.; Riccardo, V.

    2011-01-01

    A survey has been carried out into the causes of all 2309 disruptions over the last decade of JET operations. The aim of this survey was to obtain a complete picture of all possible disruption causes, in order to devise better strategies to prevent or mitigate their impact. The analysis allows the

  3. Recovery of Disruptions in Rapid Transit Networks

    NARCIS (Netherlands)

    Cadarso, L.; Marin, A.; Maroti, G.

    2013-01-01

    This paper studies the disruption management problem of rapid transit rail networks. Besides optimizing the timetable and the rolling stock schedules, we explicitly deal with the effects of the disruption on the passenger demand.We propose a two-step approach that combines an integrated optimization

  4. Disruption Management in Passenger Railway Transportation

    DEFF Research Database (Denmark)

    Groth, Julie Jespersen; Potthoff, Daniel; Clausen, Jens

    2009-01-01

    This paper deals with disruption management in passenger railway transportation. In the disruption management process, many actors belonging to different organizations play a role. In this paper we therefore describe the process itself and the roles of the different actors. Furthermore, we discus...

  5. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. G.; Krægpøth, Morten Visby; Skyt Nielsen, Helena

    identify three groups of potentially disruptive and emotionally sensitive children from detailed Danish register data: children with divorced parents, children with parents convicted of crime, and children with a psychiatric diagnosis. We find that adding potentially disruptive children lowers the academic...... achievement of peers by about 1.5-2 percent of a standard deviation....

  6. Disrupted Sleep: From Molecules to Cognition

    NARCIS (Netherlands)

    van Someren, E.J.; Cirelli, C.; Dijk, D.J.; Van Cauter, E.; Schwartz, S.; Chee, M.W.L.

    2015-01-01

    Although the functions of sleep remain to be fully elucidated, it is clear that there are far-reaching effects of its disruption, whether by curtailment for a single night, by a few hours each night over a long period, or by disruption in sleep continuity. Epidemiological and experimental studies of

  7. Disrupted Sleep : From Molecules to Cognition

    NARCIS (Netherlands)

    Van Someren, Eus J W; Cirelli, Chiara; Dijk, Derk-Jan; Van Cauter, Eve; Schwartz, Sophie; Chee, Michael W L

    2015-01-01

    UNLABELLED: Although the functions of sleep remain to be fully elucidated, it is clear that there are far-reaching effects of its disruption, whether by curtailment for a single night, by a few hours each night over a long period, or by disruption in sleep continuity. Epidemiological and

  8. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. G.; Krægpøth, Morten Visby; Nielsen, Helena Skyt

    2015-01-01

    identify three groups of potentially disruptive and emotionally sensitive children from detailed Danish register data: children with divorced parents, children with parents convicted of crime, and children with a psychiatric diagnosis. We find that adding potentially disruptive children lowers the academic...

  9. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. G.; Krægpøth, Morten Visby; Skyt Nielsen, Helena

    identify three groups of potentially disruptive and emotionally sensitive children from detailed Danish register data: children with divorced parents, children with parents convicted of crime, and children with a psychiatric diagnosis. We find that adding potentially disruptive children lowers the academic...

  10. Resistance to Disruption in a Classroom Setting

    Science.gov (United States)

    Parry-Cruwys, Diana E.; Neal, Carrie M.; Ahearn, William H.; Wheeler, Emily E.; Premchander, Raseeka; Loeb, Melissa B.; Dube, William V.

    2011-01-01

    Substantial experimental evidence indicates that behavior reinforced on a denser schedule is more resistant to disruption than is behavior reinforced on a thinner schedule. The present experiment studied resistance to disruption in a natural educational environment. Responding during familiar activities was reinforced on a multiple…

  11. Residual stresses in material processing

    Science.gov (United States)

    Kozaczek, K. J.; Watkins, T. R.; Hubbard, C. R.; Wang, Xun-Li; Spooner, S.

    Material manufacturing processes often introduce residual stresses into the product. The residual stresses affect the properties of the material and often are detrimental. Therefore, the distribution and magnitude of residual stresses in the final product are usually an important factor in manufacturing process optimization or component life prediction. The present paper briefly discusses the causes of residual stresses. It then addresses the direct, nondestructive methods of residual stress measurement by X ray and neutron diffraction. Examples are presented to demonstrate the importance of residual stress measurement in machining and joining operations.

  12. Metabolic targets of endocrine disrupting chemicals assessed by cord blood transcriptome profiling

    DEFF Research Database (Denmark)

    Remy, Sylvie; Govarts, Eva; Wens, Britt

    2016-01-01

    Early life exposure to endocrine disrupting chemicals (EDCs) has been frequently associated with impaired perinatal growth, an important risk factor for later onset of metabolic disorders. We analyzed whether the cord blood transcriptome showed early indications of alterations in metabolic...

  13. Fear conditioning, persistence of disruptive behavior and psychopathic traits: an fMRI study

    NARCIS (Netherlands)

    Cohn, M.D.; Popma, A.; van den Brink, W.; Pape, L.E.; Kindt, M.; van Domburgh, L.; Doreleijers, T.A.H.; Veltman, D.J.

    2013-01-01

    Children diagnosed with Disruptive Behavior Disorders (DBD), especially those with psychopathic traits, are at risk of developing persistent and severe antisocial behavior. Deficient fear conditioning may be a key mechanism underlying persistence, and has been associated with altered regional brain

  14. Plasma membrane disruption: repair, prevention, adaptation

    Science.gov (United States)

    McNeil, Paul L.; Steinhardt, Richard A.

    2003-01-01

    Many metazoan cells inhabit mechanically stressful environments and, consequently, their plasma membranes are frequently disrupted. Survival requires that the cell rapidly repair or reseal the disruption. Rapid resealing is an active and complex structural modification that employs endomembrane as its primary building block, and cytoskeletal and membrane fusion proteins as its catalysts. Endomembrane is delivered to the damaged plasma membrane through exocytosis, a ubiquitous Ca2+-triggered response to disruption. Tissue and cell level architecture prevent disruptions from occurring, either by shielding cells from damaging levels of force, or, when this is not possible, by promoting safe force transmission through the plasma membrane via protein-based cables and linkages. Prevention of disruption also can be a dynamic cell or tissue level adaptation triggered when a damaging level of mechanical stress is imposed. Disease results from failure of either the preventive or resealing mechanisms.

  15. Mechanistic evaluation of endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Taxvig, Camilla

    BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent for the ......BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent...... metabolising system using liver S9 mixtures or hepatic rat microsomes could be a convenient method for the incorporation of metabolic aspects into in vitro testing for endocrine disrupting effects....

  16. Neuroimaging findings in disruptive behavior disorders.

    Science.gov (United States)

    Baker, Rosalind H; Clanton, Roberta L; Rogers, Jack C; De Brito, Stéphane A

    2015-08-01

    Decades of research have shown that youths with disruptive behavior disorders (DBD) are a heterogeneous population. Over the past 20 years, researchers have distinguished youths with DBD as those displaying high (DBD/HCU) versus low (DBD/LCU) callous-unemotional (CU) traits. These traits include flat affect and reduced empathy and remorse, and are associated with more severe, varied, and persistent patterns of antisocial behavior and aggression. Conduct problems in youths with HCU and LCU are thought to reflect distinct causal vulnerabilities, with antisocial behavior in youths with DBD/HCU reflecting a predominantly genetic etiology, while antisocial behavior in youths with DBD/LCU is associated primarily with environmental influences. Here we selectively review recent functional (fMRI) and structural (sMRI) magnetic resonance imaging research on DBD, focusing particularly on the role of CU traits. First, fMRI studies examining the neural correlates of affective stimuli, emotional face processing, empathy, theory of mind, morality, and decision-making in DBD are discussed. This is followed by a review of the studies investigating brain structure and structural connectivity in DBD. Next, we highlight the need to further investigate females and the role of sex differences in this population. We conclude the review by identifying potential clinical implications of this research.

  17. Disrupted functional connectivity in adolescent obesity.

    Science.gov (United States)

    Moreno-Lopez, Laura; Contreras-Rodriguez, Oren; Soriano-Mas, Carles; Stamatakis, Emmanuel A; Verdejo-Garcia, Antonio

    2016-01-01

    Obesity has been associated with brain alterations characterised by poorer interaction between a hypersensitive reward system and a comparatively weaker prefrontal-cognitive control system. These alterations may occur as early as in adolescence, but this notion remains unclear, as no studies so far have examined global functional connectivity in adolescents with excess weight. We investigated functional connectivity in a sample of 60 adolescents with excess weight and 55 normal weight controls. We first identified parts of the brain displaying between-group global connectivity differences and then characterised the extent of the differences in functional network integrity and their association with reward sensitivity. Adolescent obesity was linked to neuroadaptations in functional connectivity within brain hubs linked to interoception (insula), emotional memory (middle temporal gyrus) and cognitive control (dorsolateral prefrontal cortex) (pFWE adolescent obesity is linked to disrupted functional connectivity in brain networks relevant to maintaining balance between reward, emotional memories and cognitive control. Our findings may contribute to reconceptualization of obesity as a multi-layered brain disorder leading to compromised motivation and control, and provide a biological account to target prevention strategies for adolescent obesity.

  18. SRC Residual fuel oils

    Science.gov (United States)

    Tewari, Krishna C.; Foster, Edward P.

    1985-01-01

    Coal solids (SRC) and distillate oils are combined to afford single-phase blends of residual oils which have utility as fuel oils substitutes. The components are combined on the basis of their respective polarities, that is, on the basis of their heteroatom content, to assure complete solubilization of SRC. The resulting composition is a fuel oil blend which retains its stability and homogeneity over the long term.

  19. Disruption and adaptation of urban transport networks from flooding

    Directory of Open Access Journals (Sweden)

    Pregnolato Maria

    2016-01-01

    Full Text Available Transport infrastructure networks are increasingly vulnerable to disruption from extreme rainfall events due to increasing surface water runoff from urbanization and changes in climate. Impacts from such disruptions typically extend far beyond the flood footprint, because of the interconnection and spatial extent of modern infrastructure. An integrated flood risk assessment couples high resolution information on depth and velocity from the CityCAT urban flood model with empirical analysis of vehicle speeds in different depths of flood water, to perturb a transport accessibility model and determine the impact of a given event on journey times across the urban area. A case study in Newcastle-upon-Tyne (UK shows that even minor flooding associate with a 1 in 10 year event can cause traffic disruptions of nearly half an hour. Two adaptation scenarios are subsequently tested (i hardening (i.e. flood protection a single major junction, (ii introduction of green roofs across all buildings. Both options have benefits in terms of reduced disruption, but for a 1 in 200 year event greening all roofs in the city provided only three times the benefit of protecting one critical road junction, highlighting the importance of understanding network attributes such as capacity and flows.

  20. Disruption of the human gut microbiota following Norovirus infection.

    Directory of Open Access Journals (Sweden)

    Adam M Nelson

    Full Text Available The gut microbiota, the collection of all bacterial members in the intestinal tract, plays a key role in health. Disruption of the indigenous microbiota by a variety of stressors, including antibiotic therapy and intestinal infections, is associated with multiple health problems. We sought to determine if infection with Norovirus disrupts the gut microbiota. Barcoded pyrosequencing of the 16S rRNA-encoding gene was used to characterize the stool microbiota in Norovirus-infected human patients (n = 38. While the microbiota in most infected patients (n = 31 resembled that seen in uninfected healthy controls, a minority of patients (n = 7 possessed a significantly altered microbiota characterized by reduced relative numbers of Bacteriodetes and a corresponding increase in Proteobacteria. In these patients, the increase in Proteobacteria was due to a single operational taxonomic unit (OTU of Escherichia coli. We cultured E. coli from Norovirus-infected patients and characterized them using PCR-ribotyping and virulence factor analysis. Multiple ribotypes were encountered, but none possessed typical virulence factors commonly carried by enteropathogenic E. coli strains. Microbiota disruption and elevated Proteobacteria were not significantly correlated to patient age, gender, sampling time following illness onset, or overall gut inflammation. These results demonstrate that some patients have a disrupted microbiota following Norovirus infection, and therefore may be at elevated risk for long-term health complications.

  1. Consequences of family disruption on children's educational outcomes in Norway.

    Science.gov (United States)

    Steele, Fiona; Sigle-Rushton, Wendy; Kravdal, Øystein

    2009-08-01

    Using high-quality data from Norwegian population registers, we examine the relationship between family disruption and children's educational outcomes. We distinguish between disruptions caused by parental divorce and paternal death and, using a simultaneous equation model, pay particular attention to selection bias in the effect of divorce. We also allow for the possibility that disruption may have different effects at different stages of a child's educational career. Our results suggest that selection on time-invariant maternal characteristics is important and works to overstate the effects of divorce on a child's chances of continuing in education. Nevertheless, the experience of marital breakdown during childhood is associated with lower levels of education, and the effect weakens with the child's age at disruption. The effects of divorce are most pronounced for the transitions during or just beyond the high school level. In models that do not allow for selection, children who experienced a father's death appear less disadvantaged than children whose parents divorced. After we control for selection, however differences in the educational qualifications of children from divorced and bereaved families narrow substantially and, at mean ages of divorce, are almost non-existent.

  2. Composition of carbonization residues

    Energy Technology Data Exchange (ETDEWEB)

    Hupfer; Leonhardt

    1943-11-30

    This report gave a record of the composition of several samples of residues from carbonization of various hydrogenation residue from processing some type of coal or tar in the Bergius process. These included Silesian bituminous coal processed at 600 atm. with iron catalyst, in one case to produce gasoline and middle oil and in another case to produce heavy oil excess, Scholven coal processed at 250 atm. with tin oxalate and chlorine catalyst, Bruex tar processed in a 10-liter oven using iron catalyst, and a pitch mixture from Welheim processed in a 10-liter over using iron catalyst. The values gathered were compared with a few corresponding values estimated for Boehlen tar and Gelsenberg coal based on several assumptions outlined in the report. The data recorded included percentage of ash in the dry residue and percentage of carbon, hydrogen, oxygen, nitrogen, chlorine, total sulfur, and volatile sulfur. The percentage of ash varied from 21.43% in the case of Bruex tar to 53.15% in the case of one of the Silesian coals. Percentage of carbon varied from 44.0% in the case of Scholven coal to 78.03% in the case of Bruex tar. Percentage of total sulfur varied from 2.28% for Bruex tar to a recorded 5.65% for one of the Silesian coals and an estimated 6% for Boehlen tar. 1 table.

  3. Crop Residue Biomass Effects on Agricultural Runoff

    Directory of Open Access Journals (Sweden)

    Damodhara R. Mailapalli

    2013-01-01

    Full Text Available High residue loads associated with conservation tillage and cover cropping may impede water flow in furrow irrigation and thus decrease the efficiency of water delivery and runoff water quality. In this study, the biomass residue effects on infiltration, runoff, and export of total suspended solids (TSS, dissolved organic carbon (DOC, sediment-associated carbon (TSS-C, and other undesirable constituents such as phosphate (soluble P, nitrate (, and ammonium ( in runoff water from a furrow-irrigated field were studied. Furrow irrigation experiments were conducted in 91 and 274 m long fields, in which the amount of residue in the furrows varied among four treatments. The biomass residue in the furrows increased infiltration, and this affected total load of DOC, TSS, and TSS-C. Net storage of DOC took place in the long but not in the short field because most of the applied water ran off in the short field. Increasing field length decreased TSS and TSS-C losses. Total load of , , and soluble P decreased with increasing distance from the inflow due to infiltration. The concentration and load of P increased with increasing residue biomass in furrows, but no particular trend was observed for and . Overall, the constituents in the runoff decreased with increasing surface cover and field length.

  4. Extracurricular activity participation moderates impact of family and school factors on adolescents' disruptive behavioural problems.

    Science.gov (United States)

    Driessens, Corine M E F

    2015-11-11

    The prevalence of problem behaviours among British adolescents has increased in the past decades. Following Erikson's psychosocial developmental theory and Bronfenbrenner's developmental ecological model, it was hypothesized that youth problem behaviour is shaped in part by social environment. The aim of this project was to explore potential protective factors within the social environment of British youth's for the presentation of disruptive behavioural problems. This study used secondary data from the Longitudinal Study of Young People in England, a cohort study of secondary school students. These data were analysed with generalized estimation equations to take the correlation between the longitudinal observations into account. Three models were built. The first model determined the effect of family, school, and extracurricular setting on presentation of disruptive behavioural problems. The second model expanded the first model by assuming extracurricular activities as protective factors that moderated the interaction between family and school factors with disruptive behavioural problems. The third model described the effect of prior disruptive behaviour on current disruptive behaviour. Associations were found between school factors, family factors, involvement in extracurricular activities and presence of disruptive behavioural problems. Results from the second generalized estimating equation (GEE) logistic regression models indicated that extracurricular activities buffered the impact of school and family factors on the presence of disruptive behavioural problems. For instance, participation in sports activities decreased the effect of bullying on psychological distress. Results from the third model indicated that prior acts of disruptive behaviour reinforced current disruptive behaviour. This study supports Erikson's psychosocial developmental theory and Bronfenbrenner's developmental ecological model; social environment did influence the presence of

  5. Perspective: delivering effective and engaging continuing medical education on physicians' disruptive behavior.

    Science.gov (United States)

    McLaren, Kimberly; Lord, Julie; Murray, Suzanne

    2011-05-01

    Education about physicians' disruptive behavior is relevant for practicing physicians, who must demonstrate competence in professionalism for maintenance of certification. In addition, physicians need to know about newer regulatory standards that define disruptive behavior and mandated processes for dealing with such behavior, as health care organizations are now charged with having formal policies addressing this issue. There is a growing literature about dealing with disruptive behavior, but it has not addressed education, including continuing medical education (CME), aimed at reducing or preventing disruptive behavior. The authors suggest specific strategies for such CME educational programs, including knowing the audience before the presentation, avoiding potential pitfalls, defusing defensiveness, and increasing audience "buy-in." They present two viewpoints from which to approach the topic of disruptive behavior, depending on the audience: "rekindling of values" and "risk reduction." The authors also recommend interactive teaching methods designed to maximize audience participation and foster self-awareness and reflection. Copyright © by the Association of American medical Colleges.

  6. Disrupting Mosquito Reproduction and Parasite Development for Malaria Control

    Science.gov (United States)

    Gabrieli, Paolo; Buckee, Caroline O.; Catteruccia, Flaminia

    2016-01-01

    The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria. When an agonist of the steroid hormone 20-hydroxyecdysone (20E) is applied to Anopheles gambiae females, which are the dominant malaria mosquito vector in Sub Saharan Africa, it substantially shortens lifespan, prevents insemination and egg production, and significantly blocks Plasmodium falciparum development, three components that are crucial to malaria transmission. Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance. PMID:27977810

  7. Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes

    DEFF Research Database (Denmark)

    Pham, Minh-Long; Kolb, H; Battelino, T

    2013-01-01

    Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes.......Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes....

  8. Quadratic residues and non-residues selected topics

    CERN Document Server

    Wright, Steve

    2016-01-01

    This book offers an account of the classical theory of quadratic residues and non-residues with the goal of using that theory as a lens through which to view the development of some of the fundamental methods employed in modern elementary, algebraic, and analytic number theory. The first three chapters present some basic facts and the history of quadratic residues and non-residues and discuss various proofs of the Law of Quadratic Reciprosity in depth, with an emphasis on the six proofs that Gauss published. The remaining seven chapters explore some interesting applications of the Law of Quadratic Reciprocity, prove some results concerning the distribution and arithmetic structure of quadratic residues and non-residues, provide a detailed proof of Dirichlet’s Class-Number Formula, and discuss the question of whether quadratic residues are randomly distributed. The text is a valuable resource for graduate and advanced undergraduate students as well as for mathematicians interested in number theory.

  9. Postinduction Minimal Residual Disease Predicts Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia With NPM1 Mutation: A Study by the Acute Leukemia French Association Group.

    Science.gov (United States)

    Balsat, Marie; Renneville, Aline; Thomas, Xavier; de Botton, Stéphane; Caillot, Denis; Marceau, Alice; Lemasle, Emilie; Marolleau, Jean-Pierre; Nibourel, Olivier; Berthon, Céline; Raffoux, Emmanuel; Pigneux, Arnaud; Rodriguez, Céline; Vey, Norbert; Cayuela, Jean-Michel; Hayette, Sandrine; Braun, Thorsten; Coudé, Marie Magdeleine; Terre, Christine; Celli-Lebras, Karine; Dombret, Hervé; Preudhomme, Claude; Boissel, Nicolas

    2017-01-10

    Purpose This study assessed the prognostic impact of postinduction NPM1-mutated ( NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission. Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classification were eligible for ASCT in first remission. Results After induction therapy, patients who did not achieve a 4-log reduction in NPM1m peripheral blood-MRD (PB-MRD) had a higher cumulative incidence of relapse (subhazard ratio [SHR], 5.83; P benefit was not observed in those with a > 4-log reduction in PB-MRD, with a significant interaction between ASCT effect and PB-MRD response ( P = .024 and .027 for disease-free survival and OS, respectively). Conclusion Our study supports the strong prognostic significance of early NPM1m PB-MRD, independent of the cytogenetic and molecular context. Moreover, NPM1m PB-MRD may be used as a predictive factor for ASCT indication.

  10. Mutations in the hydrophobic surface of an amphipathic groove of 14-3-3zeta disrupt its interaction with Raf-1 kinase.

    Science.gov (United States)

    Wang, H; Zhang, L; Liddington, R; Fu, H

    1998-06-26

    14-3-3 proteins bind to a diverse group of regulatory molecules such as Raf-1, Cbl, and c-Bcr that are involved in signal transduction pathways. The crystal structure of 14-3-3zeta reveals a conserved amphipathic groove that may mediate the association of 14-3-3 with diverse ligands. Consistently, mutations on the charged surface of the groove (Lys-49, Arg-56, and Arg-60) decrease the binding of 14-3-3zeta to the ligands tested (Zhang, L., Wang, H., Liu, D., Liddington, R., and Fu, H. (1997) J. Biol. Chem. 272, 13717-13724). Here we report that mutations that altered the hydrophobic property of the groove, V176D, L216D, L220D, and L227D, disrupted the interaction of 14-3-3zeta with Raf-1 kinase. The reduced binding of the 14-3-3zeta mutants to Raf-1 was apparently not because of gross structural changes in the mutants as judged by their ability to form dimers, by partial proteolysis profiles, and by circular dichroism analysis. These hydrophobic residues appeared to be required for the binding of 14-3-3zeta to distinct activation states of Raf-1 because mutations V176D, L216D, L220D, and L227D reduced the interaction of 14-3-3zeta with Raf-1 from both phorbol 12-myristate 13-acetate-stimulated and unstimulated Jurkat T cells. These same mutations also disrupted the association of 14-3-3zeta with other regulatory molecules such as Cbl and c-Bcr, suggesting that the hydrophobic surface of the amphipathic groove represents part of a binding site shared by a number of 14-3-3-associated proteins. The conservation of the hydrophobic residues Val-176, Leu-216, Leu-220, and Leu-227 among known 14-3-3 family members implies their general importance in ligand binding.

  11. Report on Criteria for Endocrine Disrupters

    DEFF Research Database (Denmark)

    Holbech, Henrik

    2011-01-01

    This report has been prepared by the Danish Centre on Endocrine Disrupters as a project contracted by the Danish Environmental Protection Agency. The Danish Centre on Endocrine Disrupters is an interdisciplinary scientific network without walls. The main purpose of the Centre is to build and gather....... The overall aim of this project is to provide a science based proposal for criteria for endocrine disrupters. The terms of reference for the project specify elements to be included and/or addressed when developing the criteria (Annex 1). Also, several international reports and papers dealing with assessment...

  12. The Effects of Disruption on Strategic Management

    DEFF Research Database (Denmark)

    Drejer, Anders

    2017-01-01

    , Digitalization, Globalization and much more. Furthermore, the effects of disruption are now being felt by organizations and industries all over the world. In this paper, we will try to outline and illustrate some of those effects using the case-study of an international, Danish, SME. The case company has been...... forced to face some challenges caused by disruption and in the process of doing so has changed its strategy process significantly towards a more learning based approach to strategic management. Keywords: disruption; case- study; SME; strategy process....

  13. Periodic disruptions in the MT-1 tokamak

    International Nuclear Information System (INIS)

    Zoletnik, S.

    1988-11-01

    Disruptive instabilities are common phenomena in toroidal devices, especially in tokamaks. Three types can be distinguished: internal, minor and major disruptions. Periodic minor disruptions in the MT-1 tokamak were measured systematically with values of the limiter safety factor between 4 and 10. The density limit as a function of plasma current and horizontal displacement was investigated. Precursor oscillations always appear before the instability with increasing amplitude but can be observed at the density limit with quasi-stationary amplitude. Phase correlation between precursor oscillations were measured with Mirnov coils and x-ray detectors, and they show good agreement with a simple magnetic island model. (R.P.) 11 refs.; 6 figs

  14. Visual in-pile fuel disruption experiments

    International Nuclear Information System (INIS)

    Cano, G.L.; Ostensen, R.W.; Young, M.F.

    1978-01-01

    In a loss-of-flow (LOF) accident in an LMFBR, the mode of disruption of fuel may determine the probability of a subsequent energetic excursion. To investigate these phenomena, in-pile disruption of fission-heated irradiated fuel pellets was recorded by high speed cinematography. Instead of fuel frothing or dust-cloud breakup (as used in the SAS code) massive and very rapid fuel swelling, not predicted by analytical models, occurred. These tests support massive fuel swelling as the initial mode of fuel disruption in a LOF accident. (author)

  15. Erosion products in disruption simulation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Safronov, V.; Arkhipov, N.; Bakhtin, V.; Barsuk, V.; Kurkin, S.; Mironova, E.; Toporkov, D.; Vasenin, S.; Zhitlukhin, A. [Troitsk Inst. for Innovation and Fusion Research, Troisk, Moscow region (Russian Federation); Arkhipov, I. [Inst. of Physical Chemistry, Russian Academy of Science, Moscow (Russian Federation); Werle, H.; Wuerz, H. [Forschungszentrum Karlsruhe (Germany)

    1998-07-01

    Erosion of divertor materials under tokamak disruption event presents a serious problem of ITER technology. Erosion restricts the divertor lifetime and leads to production of redeposited layers of the material retaining large amount of tritium, which is a major safety issue for future fusion reactor. Since ITER disruptive heatloads are not achievable in existing tokamaks, material erosion is studied in special simulation experiments. Till now the simulation experiments have focused mainly on investigation of shielding effect and measurement of erosion rate. In the present work the properties of eroded and redeposited graphite are studied under condition typical for hard ITER disruption. (author)

  16. Disruptions and Their Mitigation in TEXTOR

    International Nuclear Information System (INIS)

    Finken, K.H.; Jaspers, R.; Kraemer-Flecken, A.; Savtchkov, A.; Lehnen, M.; Waidmann, G.

    2005-01-01

    Disruptions remain a major concern for tokamak devices, particularly for large machines. The critical issues are the induced (halo) currents and the resulting forces, the excessive heating of exposed surfaces by the instantaneous power release, and the possible occurrence of highly energetic runaway electrons. The key topics of the investigations on TEXTOR in the recent years concerned (a) the power deposition pattern recorded by a fast infrared scanner, (b) the runaway generation measured by synchrotron radiation in the infrared spectral region, (c) method development for 'healing' discharges that are going to disrupt, and (d) massive gas puffing for mitigating the adverse effects of disruptions

  17. Residual generator for cardiovascular anomalies detection

    KAUST Repository

    Belkhatir, Zehor

    2014-06-01

    This paper discusses the possibility of using observer-based approaches for cardiovascular anomalies detection and isolation. We consider a lumped parameter model of the cardiovascular system that can be written in a form of nonlinear state-space representation. We show that residuals that are sensitive to variations in some cardiovascular parameters and to abnormal opening and closure of the valves, can be generated. Since the whole state is not easily available for measurement, we propose to associate the residual generator to a robust extended kalman filter. Numerical results performed on synthetic data are provided.

  18. Sharing Residual Liability

    DEFF Research Database (Denmark)

    Carbonara, Emanuela; Guerra, Alice; Parisi, Francesco

    2016-01-01

    Economic models of tort law evaluate the efficiency of liability rules in terms of care and activity levels. A liability regime is optimal when it creates incentives to maximize the value of risky activities net of accident and precaution costs. The allocation of primary and residual liability...... the virtues and limits of loss-sharing rules in generating optimal (second-best) incentives and allocations of risk. We find that loss sharing may be optimal in the presence of countervailing policy objectives, homogeneous risk avoiders, and subadditive risk, which potentially offers a valuable tool...

  19. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

    Energy Technology Data Exchange (ETDEWEB)

    Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

    2015-09-15

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP

  20. [Technological process of cell disruption for extracting astaxanthin from Phaffia rhodozyma by acid method under autoclave conditions].

    Science.gov (United States)

    Lu, Baoju; Xiao, Anfeng; Lil, Lijun; Ni, Hui; Cai, Huinong; Su, Wenjin

    2008-07-01

    Phaffia rhodozyma is one of the organisms for production of astaxanthin, and the key process for extracting intracellular astaxanthin is cell disruption. In this work, cell disruption for extracting astaxanthin from Phaffia rhodozyma was studied with autoclave method at low acid concentration. The optimum disrupting conditions were: autoclave pressure 0.1 MPa, 121 degrees C; hydrochloric acid concentration 0.5 mol/L; liquid to material ratio (V/W) 30 mL/g dry cell weight and disruption time 2 min. Under the optimum conditions, medium scale experiment showed that astaxanthin and total carotenoids recovery from Phaffia rhodozyma were (84.8 +/- 3.2)% and (93.3 +/- 2)%, respectively. This new method can lead to no poisonous residues and get high extraction yield, which have good prospects to be put into industrial production.

  1. Sustainable System for Residual Hazards Management

    International Nuclear Information System (INIS)

    Kevin M. Kostelnik; James H. Clarke; Jerry L. Harbour

    2004-01-01

    Hazardous, radioactive and other toxic substances have routinely been generated and subsequently disposed of in the shallow subsurface throughout the world. Many of today's waste management techniques do not eliminate the problem, but rather only concentrate or contain the hazardous contaminants. Residual hazards result from the presence of hazardous and/or contaminated material that remains on-site following active operations or the completion of remedial actions. Residual hazards pose continued risk to humans and the environment and represent a significant and chronic problem that require continuous long-term management (i.e. >1000 years). To protect human health and safeguard the natural environment, a sustainable system is required for the proper management of residual hazards. A sustainable system for the management of residual hazards will require the integration of engineered, institutional and land-use controls to isolate residual contaminants and thus minimize the associated hazards. Engineered controls are physical modifications to the natural setting and ecosystem, including the site, facility, and/or the residual materials themselves, in order to reduce or eliminate the potential for exposure to contaminants of concern (COCs). Institutional controls are processes, instruments, and mechanisms designed to influence human behavior and activity. System failure can involve hazardous material escaping from the confinement because of system degradation (i.e., chronic or acute degradation) or by external intrusion of the biosphere into the contaminated material because of the loss of institutional control. An ongoing analysis of contemporary and historic sites suggests that the significance of the loss of institutional controls is a critical pathway because decisions made during the operations/remedial action phase, as well as decisions made throughout the residual hazards management period, are key to the long-term success of the prescribed system. In fact

  2. Circulating Levels of MicroRNA from Children with Newly Diagnosed Type 1 Diabetes and Healthy Controls: Evidence That miR-25 Associates to Residual Beta-Cell Function and Glycaemic Control during Disease Progression

    Directory of Open Access Journals (Sweden)

    Lotte B. Nielsen

    2012-01-01

    Full Text Available This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D. We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n = 275 and 129, resp. and one control group (n = 151. We identified twelve upregulated human miRNAs in T1D patients (miR-152, miR-30a-5p, miR-181a, miR-24, miR-148a, miR-210, miR-27a, miR-29a, miR-26a, miR-27b, miR-25, miR-200a; several of these miRNAs were linked to apoptosis and beta-cell networks. Furthermore, we identified miR-25 as negatively associated with residual beta-cell function (est.: −0.12, P = 0.0037, and positively associated with glycaemic control (HbA1c (est.: 0.11, P = 0.0035 3 months after onset. In conclusion this study demonstrates that miR-25 might be a “tissue-specific” miRNA for glycaemic control 3 months after diagnosis in new onset T1D children and therefore supports the role of circulating miRNAs as predictive biomarkers for tissue physiopathology and potential intervention targets.

  3. A novel approach using actigraphy to quantify the level of disruption of sleep by in-home polysomnography: the MrOS Sleep Study: Sleep disruption by polysomnography.

    Science.gov (United States)

    Blackwell, Terri; Paudel, Misti; Redline, Susan; Ancoli-Israel, Sonia; Stone, Katie L

    2017-04-01

    The "first-night effect" of polysomnography (PSG) has been previously studied; however, the ability to quantify the sleep disruption level has been confounded with the use of PSG on all nights. We used actigraphy to quantify disruption level and examined characteristics associated with disruption. Totally, 778 older men (76.2 ± 5.4 years) from a population-based study at six US centers underwent one night of in-home PSG. Actigraphy was performed on the PSG night and three subsequent nights. Actigraphically measured total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep onset latency (SOL) from the PSG night and subsequent nights were compared. Linear regression models were used to examine the association of characteristics and sleep disruption. On average, sleep on the PSG night was worse than the following night (p disruption on the PSG night included older age, higher apnea-hypopnea index, worse neuromuscular function, and more depressive symptoms. Minorities and men with excessive daytime sleepiness slept somewhat better on the PSG night. Among older men, there was sleep disruption on the PSG night, which may lead to sleep time underestimation. The increase of sleep on the night after the PSG suggests that data from the second monitoring may overestimate sleep. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The Logic of Digital Platform Disruption

    DEFF Research Database (Denmark)

    Kazan, Erol; Tan, Chee-Wee; Lim, Eric T. K.

    Digital platforms are disruptive IT artifacts, because they facilitate the quick release of innovative platform derivatives from third parties (e.g., apps). This study endeavours to unravel the disruptive potential, caused by distinct designs and configurations of digital platforms on market...... environments. We postulate that the disruptive potential of digital platforms is determined by the degree of alignment among the business, technology and platform profiles. Furthermore, we argue that the design and configuration of the aforementioned three elements dictates the extent to which open innovation...... is permitted. To shed light on the disruptive potential of digital platforms, we opted for payment platforms as our unit of analysis. Through interviews with experts and payment providers, we seek to gain an in-depth appreciation of how contemporary digital payment platforms are designed and configured...

  5. Runaway electron generation in tokamak disruptions

    Energy Technology Data Exchange (ETDEWEB)

    Helander, P. [EURATOM/UKAEA Fusion Association, Culham Science Centre, Abingdon (United Kingdom); Andersson, F.; Fulop, T.; Smith, T.H.; Anderson, D.; Lisak, M. [Chalmers Univ. of Technology, Dept. of Electromagnetics, Goteborg (Sweden); Eriksson, L.G. [Euratom-CEA, Centre d' Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee

    2004-07-01

    The time evolution of the plasma current during a tokamak disruption is calculated by solving the equations for runaway electron production simultaneously with the induction equation for the toroidal electric field. The resistive diffusion time in a post-disruption plasma is typically comparable to the runaway avalanche growth time. Accordingly, the toroidal electric field induced after the thermal quench of a disruption diffuses radially through the plasma at the same time as it accelerates runaway electrons, which in turn back-react on the electric field. When these processes are accounted for in a self-consistent way, it is found that (1) the efficiency and time scale of runaway generation agrees with JET experiments; (2) the runaway current profile typically becomes more peaked than the pre-disruption current profile; and (3) can easily become radially in the shape of filaments. It is also shown that higher runaway electron generation is expected if the thermal quench is sufficiently fast. (authors)

  6. Bioenergy from sisal residues

    Energy Technology Data Exchange (ETDEWEB)

    Jungersen, G. [Dansk Teknologisk Inst. (Denmark); Kivaisi, A.; Rubindamayugi, M. [Univ. of Dar es Salaam (Tanzania, United Republic of)

    1998-05-01

    The main objectives of this report are: To analyse the bioenergy potential of the Tanzanian agro-industries, with special emphasis on the Sisal industry, the largest producer of agro-industrial residues in Tanzania; and to upgrade the human capacity and research potential of the Applied Microbiology Unit at the University of Dar es Salaam, in order to ensure a scientific and technological support for future operation and implementation of biogas facilities and anaerobic water treatment systems. The experimental work on sisal residues contains the following issues: Optimal reactor set-up and performance; Pre-treatment methods for treatment of fibre fraction in order to increase the methane yield; Evaluation of the requirement for nutrient addition; Evaluation of the potential for bioethanol production from sisal bulbs. The processing of sisal leaves into dry fibres (decortication) has traditionally been done by the wet processing method, which consumes considerable quantities of water and produces large quantities of waste water. The Tanzania Sisal Authority (TSA) is now developing a dry decortication method, which consumes less water and produces a waste product with 12-15% TS, which is feasible for treatment in CSTR systems (Continously Stirred Tank Reactors). (EG)

  7. Rare Earth Element Phases in Bauxite Residue

    Directory of Open Access Journals (Sweden)

    Johannes Vind

    2018-02-01

    Full Text Available The purpose of present work was to provide mineralogical insight into the rare earth element (REE phases in bauxite residue to improve REE recovering technologies. Experimental work was performed by electron probe microanalysis with energy dispersive as well as wavelength dispersive spectroscopy and transmission electron microscopy. REEs are found as discrete mineral particles in bauxite residue. Their sizes range from <1 μm to about 40 μm. In bauxite residue, the most abundant REE bearing phases are light REE (LREE ferrotitanates that form a solid solution between the phases with major compositions (REE,Ca,Na(Ti,FeO3 and (Ca,Na(Ti,FeO3. These are secondary phases formed during the Bayer process by an in-situ transformation of the precursor bauxite LREE phases. Compared to natural systems, the indicated solid solution resembles loparite-perovskite series. LREE particles often have a calcium ferrotitanate shell surrounding them that probably hinders their solubility. Minor amount of LREE carbonate and phosphate minerals as well as manganese-associated LREE phases are also present in bauxite residue. Heavy REEs occur in the same form as in bauxites, namely as yttrium phosphates. These results show that the Bayer process has an impact on the initial REE mineralogy contained in bauxite. Bauxite residue as well as selected bauxites are potentially good sources of REEs.

  8. Isolation of residuals using trend surface analysis to magnetic data ...

    African Journals Online (AJOL)

    Polynomial surfaces of various degrees are fitted to a magnetic data of Awo area, southwestern Nigeria with the aim of isolating the residuals of the area associated with mineralogy. The fourth degree surface correlates better with the magnetic map of the study area. The residualized data were obtained by subtracting the ...

  9. Quantitative Analysis of Oxytetracycline Residue in Beef and ...

    African Journals Online (AJOL)

    This study showed that a high proportion of beef and chicken consumed in the cities contained violative levels of oxytetracycline residue arising possibly from indiscriminate antibiotics usage in Nigeria livestock industry. These could predispose meat consumers to the associated health risks of antibiotic residue. Regulatory ...

  10. An intention-activation account of residual switch costs

    NARCIS (Netherlands)

    De Jong, R; Monsell, S; Driver, J

    2000-01-01

    Residual switch costs are performance costs associated with a shift of task that persist even when there is ample time to prepare in advance for the new task. I present a mixture-model approach for evaluating the contributions of two possible causes of residual switch costs: (1) failures to take

  11. Research Progress on Furfural Residues Recycling : A Literature Review

    NARCIS (Netherlands)

    Dai, Chun'ai; Liu, Bo; Girisuta, B.; Heeres, H.J.

    2010-01-01

    Millions of tons of furfural residues from the furfural industry are produced every year in China. Proper recycling of these residues is highly desirable as it may reduce associated environmental problems and increase the economic viability of the furfural industry. Research progress on furfural

  12. Disruption Management in Passenger Railway Transportation

    DEFF Research Database (Denmark)

    Jespersen-Groth, Julie; Potthoff, Daniel; Clausen, Jens

    This paper deals with disruption management in passenger railway transportation. In the disruption management process, many actors belonging to different organizations play a role. In this paper we therefore describe the process itself and the roles of the different actors. Furthermore, we discus...... for related problems in the airline world are discussed as well. Finally, we address the integration of the re-scheduling processes of the timetable, and the resources rolling stock and crew....

  13. On root class residuality of HNN-extensions

    International Nuclear Information System (INIS)

    Tieudjo, D.

    2004-08-01

    A sufficient condition or root-class residuality of HNN-extensions with root-class residual base group is proven; namely if G = -1 1Ht = K, φ> is the HNN-extension with base group A, stable letter t and associated subgroups H and K via the isomorphism φ, then G is root-class residual if group A is root-class residual and there exists a homomorphism σ of group G onto some group of a root-class such that σ is one-to-one on H. For the particular case when H = K and σ is the identical map, it is shown that G is root-class residual if and only if A is root-class residual and subgroup H of A is root-class separable. These results are generalized to multiple HNN-extensions. (author)

  14. BINARY DISRUPTION BY MASSIVE BLACK HOLES: HYPERVELOCITY STARS, S STARS, AND TIDAL DISRUPTION EVENTS

    Energy Technology Data Exchange (ETDEWEB)

    Bromley, Benjamin C. [Department of Physics and Astronomy, University of Utah, 115 S 1400 E, Rm 201, Salt Lake City, UT 84112 (United States); Kenyon, Scott J.; Geller, Margaret J.; Brown, Warren R., E-mail: bromley@physics.utah.edu, E-mail: skenyon@cfa.harvard.edu, E-mail: mgeller@cfa.harvard.edu, E-mail: wbrown@cfa.harvard.edu [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States)

    2012-04-20

    We examine whether disrupted binary stars can fuel black hole growth. In this mechanism, tidal disruption produces a single hypervelocity star (HVS) ejected at high velocity and a former companion star bound to the black hole. After a cluster of bound stars forms, orbital diffusion allows the black hole to accrete stars by tidal disruption at a rate comparable to the capture rate. In the Milky Way, HVSs and the S star cluster imply similar rates of 10{sup -5} to 10{sup -3} yr{sup -1} for binary disruption. These rates are consistent with estimates for the tidal disruption rate in nearby galaxies and imply significant black hole growth from disrupted binaries on 10 Gyr timescales.

  15. Airline Disruption Management - Perspectives, Experiences and Outlook

    DEFF Research Database (Denmark)

    Kohl, Niklas; Larsen, Allan; Larsen, Jesper

    2004-01-01

    Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused by for ex......Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused...... by for example severe weather, technical problems and crew sickness. Thus, the field of Airline Disruption Management has emerged within the past few years. The increased focus on cutting cost at the major airlines has intensified the interest in the development of new and cost e cient methods to handle airline...... disruptions. The purpose of this paper is twofold. In the first part it o ers an introduction to airline disruption management, provides the readers with a description of the planning processes and delivers a detailed overview of the numerous aspects of airline disruption management. In the second part we...

  16. Airline Disruption Management - Perspectives, Experiences and Outlook

    DEFF Research Database (Denmark)

    Kohl, Niklas; Larsen, Allan; Larsen, Jesper

    2007-01-01

    Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused by for ex......Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused...... by for example severe weather, technical problems and crew sickness. Thus, the field of Airline Disruption Management has emerged within the past few years. The increased focus on cutting cost at the major airlines has intensified the interest in the development of new and cost efficient methods to handle...... airline disruptions. The purpose of this paper is twofold. In the first part it offers an introduction to airline disruption management provides the readers with a description of the planning processes and delivers a detailed overview of the numerous aspects of airline disruption management. In the second...

  17. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    Science.gov (United States)

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2008-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days. PMID:18078723

  18. Endocrine disrupting chemicals: harmful substances and how to test them

    Directory of Open Access Journals (Sweden)

    Olea-Serrano Nicolás

    2002-01-01

    Full Text Available This paper presents an analysis of the opinions of different groups from: scientists, international regulatory bodies, non-governmental organizations and industry; with an interest in the problem of identifying chemical substances with endocrine disrupting activity. There is also discussion of the consequences that exposure to endocrine disruptors may have for human health, considering concrete issues related to: the estimation of risk; the tests that must be used to detect endocrine disruption; the difficulties to establish an association between dose, time of exposure, individual susceptibility, and effect; and the attempts to create a census of endocrine disruptors. Finally, it is proposed that not all hormonal mimics should be included under the single generic denomination of endocrine disruptors.

  19. Disruption of gut homeostasis by opioids accelerates HIV disease progression

    Directory of Open Access Journals (Sweden)

    Jingjing eMeng

    2015-06-01

    Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

  20. Disruptive Logic Architectures and Technologies From Device to System Level

    CERN Document Server

    Gaillardon, Pierre-Emmanuel; Clermidy, Fabien

    2012-01-01

    This book discusses the opportunities offered by disruptive technologies to overcome the economical and physical limits currently faced by the electronics industry. It provides a new methodology for the fast evaluation of an emerging technology from an architectural perspective and discusses the implications from simple circuits to complex architectures. Several technologies are discussed, ranging from 3-D integration of devices (Phase Change Memories, Monolithic 3-D, Vertical NanoWires-based transistors) to dense 2-D arrangements (Double-Gate Carbon Nanotubes, Sublithographic Nanowires, Lithographic Crossbar arrangements). Novel architectural organizations, as well as the associated tools, are presented in order to explore this freshly opened design space. Describes a novel architectural organization for future reconfigurable systems; Includes a complete benchmarking toolflow for emerging technologies; Generalizes the description of reconfigurable circuits in terms of hierarchical levels; Assesses disruptive...

  1. Ecosystem regime shifts disrupt trophic structure.

    Science.gov (United States)

    Hempson, Tessa N; Graham, Nicholas A J; MacNeil, M Aaron; Hoey, Andrew S; Wilson, Shaun K

    2018-01-01

    Regime shifts between alternative stable ecosystem states are becoming commonplace due to the combined effects of local stressors and global climate change. Alternative states are characterized as substantially different in form and function from pre-disturbance states, disrupting the delivery of ecosystem services and functions. On coral reefs, regime shifts are typically characterized by a change in the benthic composition from coral to macroalgal dominance. Such fundamental shifts in the benthos are anticipated to impact associated fish communities that are reliant on the reef for food and shelter, yet there is limited understanding of how regime shifts propagate through the fish community over time, relative to initial or recovery conditions. This study addresses this knowledge gap using long-term data of coral reef regime shifts and recovery on Seychelles reefs following the 1998 mass bleaching event. It shows how trophic structure of the reef fish community becomes increasingly dissimilar between alternative reef ecosystem states (regime-shifted vs. recovering) with time since disturbance. Regime-shifted reefs developed a concave trophic structure, with increased biomass in base trophic levels as herbivorous species benefitted from increased algal resources. Mid trophic level species, including specialists such as corallivores, declined with loss of coral habitat, while biomass was retained in upper trophic levels by large-bodied, generalist invertivores. Recovering reefs also experienced an initial decline in mid trophic level biomass, but moved toward a bottom-heavy pyramid shape, with a wide range of feeding groups (e.g., planktivores, corallivores, omnivores) represented at mid trophic levels. Given the importance of coral reef fishes in maintaining the ecological function of coral reef ecosystems and their associated fisheries, understanding the effects of regime shifts on these communities is essential to inform decisions that enhance ecological

  2. Putative effects of endocrine disrupters on pubertal development in the human

    DEFF Research Database (Denmark)

    Teilmann, Grete; Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    Pubertal development is regulated by gonadotrophins and sex hormones. There has been a clear secular trend in the timing of puberty during the last century, puberty becoming earlier. Although improved nutrition is assumed to be the cause, this could partly be associated with exposure to so......-called endocrine disrupters. Precocious puberty has been described in several case reports of accidental exposure to oestrogenic compounds in cosmetic products, food and pharmaceuticals. Local epidemics of premature thelarche have also been suggested to be linked to endocrine disrupters. Children adopted from...... developing countries to industrialized countries often develop precocious puberty. Not only precocious puberty, but also delayed puberty can, theoretically, be associated with exposure to endocrine disrupters. While it is very plausible that endocrine disrupters may disturb pubertal development...

  3. MHD stability, operational limits and disruptions

    International Nuclear Information System (INIS)

    1999-01-01

    The present physics understandings of magnetohydrodynamic (MHD) stability of tokamak plasmas, the threshold conditions for onset of MHD instability, and the resulting operational limits on attainable plasma pressure (beta limit) and density (density limit), and the consequences of plasma disruption and disruption related effects are reviewed and assessed in the context of their application to a future DT burning reactor prototype tokamak experiment such as ITER. The principal considerations covered within the MHD stability and beta limit assessments are (i) magnetostatic equilibrium, ideal MHD stability and the resulting ideal MHD beta limit; (ii) sawtooth oscillations and the coupling of sawtooth activity to other types of MHD instability; (iii) neoclassical island resistive tearing modes and the corresponding limits on beta and energy confinement; (iv) wall stabilization of ideal MHD instabilities and resistive wall instabilities; (v) mode locking effects of non-axisymmetric error fields; (vi) edge localized MHD instabilities (ELMs, etc.); and (vii) MHD instabilities and beta/pressure gradient limits in plasmas with actively modified current and magnetic shear profiles. The principal considerations covered within the density limit assessments are (i) empirical density limits; (ii) edge power balance/radiative density limits in ohmic and L-mode plasmas; and (iii) edge parameter related density limits in H-mode plasmas. The principal considerations covered in the disruption assessments are (i) disruption causes, frequency and MHD instability onset; (ii) disruption thermal and current quench characteristics; (iii) vertical instabilities (VDEs), both before and after disruption, and plasma and in-vessel halo currents; (iv) after disruption runaway electron formation, confinement and loss; (v) fast plasma shutdown (rapid externally initiated dissipation of plasma thermal and magnetic energies); (vi) means for disruption avoidance and disruption effect mitigation; and

  4. Percutaneous cerclage wiring, does it disrupt femoral blood supply? A cadaveric injection study.

    Science.gov (United States)

    Apivatthakakul, T; Phaliphot, J; Leuvitoonvechkit, S

    2013-02-01

    A percutaneous cerclage wiring technique has been developed to reduce iatrogenic soft tissue and vascular disruption associated with classic cerclage fixation. The purpose of this study was to evaluate the extent of femoral vascular disruption resulting iatrogenically from the application of two percutaneous cerclage wire loops. Pairs of cerlage wire loops were percutaneously inserted on 18 fresh cadaveric femurs. The position of the wire loops varied. The wire loops were either inserted 10 and 15cm, 10 and 20cm, or 15 and 20cm distal to the tip of the greater trochanter. Each study group had 6 cadavers. Contralateral femurs without cerclage wiring were used as controls. Liquid contrast-gelatin was injected into the common femoral artery. Using axial and 3D CT scan images the superficial femoral artery (SFA), deep femoral artery (DFA), perforating arteries and their anastomotic patterns as well as endosteal perfusion were identified and their patency was graded. Percutaneous cerclage wiring did not disrupt femoral endosteal blood supply and maintained the integrity of all of the superficial femoral arteries. Four specimens demonstrated maintenance of all 4 perforators, 11 showed disruption of 1 perforator, and 3 showed disruption of 2 perforators. One deep femoral artery was disrupted after its first perforator branched off; however, perfusion was maintained by fill from an alternative anastamosis. There was no significant difference between disruption of deep femoral arteries and perforating arteries (P=1.000), location of wiring (P=0.905) or spacing between wire loops (P=1.000). Percutaneous cerclage wiring resulted in minimal disruption of the femoral blood supply. When partial disruption occurred the SFA, DFA, and their associated perforators compensated to maintain femoral perfusion through their anastomoses. The location of the cerclage wire and the distance between the wire loops in the proximal femur showed no significant difference in the rate of

  5. Mechanical algal disruption for efficient biodiesel extraction

    Science.gov (United States)

    Krehbiel, Joel David

    Biodiesel from algae provides several benefits over current biodiesel feedstocks, but the energy requirements of processing algae into a useable fuel are currently so high as to be prohibitive. One route to improving this is via disruption of the cells prior to lipid extraction, which can significantly increase energy recovery. Unfortunately, several obvious disruption techniques require more energy than can be gained. This dissertation examines the use of microbubbles to improve mechanical disruption of algal cells using experimental, theoretical, and computational methods. New laboratory experiments show that effective ultrasonic disruption of algae is achieved by adding microbubbles to an algal solution. The configuration studied flows the solution through a tube and insonifies a small section with a high-pressure ultrasound wave. Previous biomedical research has shown effective cell membrane damage on animal cells with similar methods, but the present research is the first to extend such study to algal cells. Results indicate that disruption increases with peak negative pressure between 1.90 and 3.07 MPa and with microbubble concentration up to 12.5 x 107 bubbles/ml. Energy estimates of this process suggest that it requires only one-fourth the currently most-efficient laboratory-scale disruption process. Estimates of the radius near each bubble that causes disruption (i.e. the disruption radius) suggest that it increases with peak negative pressure and is near 9--20 microm for all cases tested. It is anticipated that these procedures can be designed for better efficiency and efficacy, which will be facilitated by identifying the root mechanisms of the bubble-induced disruption. We therefore examine whether bubble expansion alone creates sufficient cell deformation for cell rupture. The spherically-symmetric Marmottant model for bubble dynamics allows estimation of the flow regime under experimental conditions. Bubble expansion is modeled as a point source of

  6. Erasing Fear : Effect of Disrupting Fear Memory Reconsolidation on Central and Peripheral Nervous System Activity

    OpenAIRE

    Ågren, Thomas

    2012-01-01

    Fear memories, here defined as learned associations between a stimulus and a physiological fear reaction, are formed through fear conditioning. In animals, fear memories, present in the lateral amygdala, undergo reconsolidation after recall. Moreover, this reconsolidation process can be disrupted both pharmacologically and behaviourally, resulting in a reduced fear response to the stimulus. This thesis examines the attenuation of fear memories by disrupting reconsolidation in humans, using me...

  7. Marine Tar Residues: a Review

    OpenAIRE

    Warnock, April M.; Hagen, Scott C.; Passeri, Davina L.

    2015-01-01

    Marine tar residues originate from natural and anthropogenic oil releases into the ocean environment and are formed after liquid petroleum is transformed by weathering, sedimentation, and other processes. Tar balls, tar mats, and tar patties are common examples of marine tar residues and can range in size from millimeters in diameter (tar balls) to several meters in length and width (tar mats). These residues can remain in the ocean environment indefinitely, decomposing or becoming buried in ...

  8. The time course of ongoing activity during neuritis and following axonal transport disruption.

    Science.gov (United States)

    Satkeviciute, Ieva; Goodwin, George; Bove, Geoffrey M; Dilley, Andrew

    2018-02-21

    Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons, and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS, but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or non-inflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Since it is proposed that AMS underlies mechanically-induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms.

  9. Chronic photoperiod disruption does not increase vulnerability to focal cerebral ischemia in young normotensive rats.

    Science.gov (United States)

    Ku Mohd Noor, Ku Mastura; Wyse, Cathy; Roy, Lisa A; Biello, Stephany M; McCabe, Christopher; Dewar, Deborah

    2017-11-01

    Photoperiod disruption, which occurs during shift work, is associated with changes in metabolism or physiology (e.g. hypertension and hyperglycaemia) that have the potential to adversely affect stroke outcome. We sought to investigate if photoperiod disruption affects vulnerability to stroke by determining the impact of photoperiod disruption on infarct size following permanent middle cerebral artery occlusion. Adult male Wistar rats (210-290 g) were housed singly under two different light/dark cycle conditions ( n = 12 each). Controls were maintained on a standard 12:12 light/dark cycle for nine weeks. For rats exposed to photoperiod disruption, every three days for nine weeks, the lights were switched on 6 h earlier than in the previous photoperiod. T 2 -weighted magnetic resonance imaging was performed at 48 h after middle cerebral artery occlusion. Disruption of photoperiod in young healthy rats for nine weeks did not alter key physiological variables that can impact on ischaemic damage, e.g. blood pressure and blood glucose immediately prior to middle cerebral artery occlusion. There was no effect of photoperiod disruption on infarct size after middle cerebral artery occlusion. We conclude that any potentially adverse effect of photoperiod disruption on stroke outcome may require additional factors such as high fat/high sugar diet or pre-existing co-morbidities.

  10. Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice.

    Science.gov (United States)

    Zhao, Bingxia; Chen, Yihan; Liu, Jinfeng; Zhang, Li; Wang, Jing; Yang, Yali; Lv, Qing; Xie, Mingxing

    2018-01-12

    To investigate the effects of the microbubble (MB) dose, mechanism index (MI) and sonication duration on blood-brain barrier (BBB) disruption induced by diagnostic ultrasound combined with MBs as well as to investigate the potential molecular mechanism. The extent of BBB disruption increased with MB dose, MI and sonication duration. A relatively larger extent of BBB disruption associated with minimal tissue damage was achieved by an appropriate MB dose and ultrasound exposure parameters with diagnostic ultrasound. Decreased expression of ZO-1, occludin and claudin-5 were correlated with disruption of the BBB, as confirmed by paracellular passage of the tracer lanthanum nitrate into the brain parenchyma after BBB disruption. These findings indicated that this technique is a promising tool for promoting brain delivery of diagnostic and therapeutic agents in the diagnosis and treatment of brain diseases. The extent of BBB disruption was qualitatively assessed by Evans blue (EB) staining and quantitatively analyzed by an EB extravasation measurement. A histological examination was performed to evaluate tissue damage. Expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5 was determined by western blotting analysis and immunohistofluorescence. Transmission electron microscopy was performed to observe ultrastructure changes of TJs after BBB disruption.

  11. Effect of music on mealtime disruptions.

    Science.gov (United States)

    Hooper, Jeff; Carson, Derek; Lindsay, Bill

    People with learning disabilities can disrupt mealtimes with non-cooperative, aggressive and self-injurious behaviours that challenge other people to tolerate and manage them. These behaviours appear to arise because the proximity of other people, and the heightened activity and noise of a dining room, causes anxiety and agitation. To examine how delivering calming background music via headphones affected anxiety-driven behaviours that disrupted mealtimes. A sample of 30 adults with mild, moderate or severe learning disabilities were videotaped during mealtimes on two consecutive days. On the first day, half the group ate without any calming music while the other half sat opposite them wearing earphones and listening to calming music. On the second day, the non-music and music groups swapped around. Of the participants who tolerated the earphones, only three showed disruptive behaviour; all three had been sitting at the table waiting for their food. With so few examples, meaningful inferential analysis was not possible. However, there were signs that calming music had a positive effect on disruptive mealtime behaviours. It eliminated physical harm, complaining and verbal repetition in one person, and stopped another from shouting/swearing. It also reduced the incidence of shouting/swearing, restlessness and vocalising. Calming music and reduced waiting at tables for food may reduce disruptive behaviours.

  12. Aerial energetic residue data from JBER C4 testing

    Data.gov (United States)

    U.S. Environmental Protection Agency — Aerially-collected energetic residues from surface detonation of C4. This dataset is associated with the following publication: Walsh, M., B. Gullett, M. Walsh, M....

  13. Disrupted functional connectome in antisocial personality disorder.

    Science.gov (United States)

    Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

    2017-08-01

    Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD.

  14. Disruptive Intelligence - How to gather Information to deal with disruptive innovations

    NARCIS (Netherlands)

    Vriens, D.J.; Solberg Søilen, K.

    2014-01-01

    Disruptive innovations are innovations that have the capacity to transform a whole business into one with products that are more accessible and affordable (cf. Christensen et al. 2009). As Christensen et al. argue no business is immune to such disruptive innovations. If these authors are right, it

  15. Evaluation of residue-residue contact predictions in CASP9

    KAUST Repository

    Monastyrskyy, Bohdan

    2011-01-01

    This work presents the results of the assessment of the intramolecular residue-residue contact predictions submitted to CASP9. The methodology for the assessment does not differ from that used in previous CASPs, with two basic evaluation measures being the precision in recognizing contacts and the difference between the distribution of distances in the subset of predicted contact pairs versus all pairs of residues in the structure. The emphasis is placed on the prediction of long-range contacts (i.e., contacts between residues separated by at least 24 residues along sequence) in target proteins that cannot be easily modeled by homology. Although there is considerable activity in the field, the current analysis reports no discernable progress since CASP8.

  16. Tracking Effects of Problematic Social Networking on Adolescent Psychopathology: The Mediating Role of Sleep Disruptions.

    Science.gov (United States)

    Vernon, Lynette; Modecki, Kathryn L; Barber, Bonnie L

    2017-01-01

    Concerns are growing about adolescents' problematic social networking and possible links to depressed mood and externalizing behavior. Yet there remains little understanding of underlying processes that may account for these associations, including the mediating role of sleep disruption. This study tests this putative mediating process and examines change in problematic social networking investment and disrupted sleep, in relation to change in depressed mood and externalizing behavior. A sample of 874 students (41% male; 57.2% Caucasian; baseline M age = 14.4 years) from 27 high schools were surveyed. Participants' problematic social networking, sleep disruption, and psychopathology (depressed mood, externalizing behaviors) were measured annually over 3 years. Longitudinal mediation was tested using latent trajectories of problematic social networking use, sleep disruption, and psychopathology. Both problematic social networking and sleep disruption underwent positive linear growth over time. Adolescents who increasingly invested in social networking reported increased depressed mood, with around 53% of this association explained by the indirect effect of increased sleep disruptions. Further, adolescents who increasingly invested in social networking also reported increased externalizing behavior; some of this relation was explained (13%) via increased sleep disruptions. However an alternative model in which increased externalizing was associated with increased social networking, mediated by sleep disruptions, indicated a reciprocal relation of similar magnitude. It is important for parents, teachers, and psychologists to minimize the negative effects of social networking on adolescents' psychopathology. Interventions should potentially target promoting healthy sleep habits through reductions in social networking investment and rescheduling usage away from bedtime.

  17. Formation and termination of runaway beams in ITER disruptions

    Science.gov (United States)

    Martín-Solís, J. R.; Loarte, A.; Lehnen, M.

    2017-06-01

    A self-consistent analysis of the relevant physics regarding the formation and termination of runaway beams during mitigated disruptions by Ar and Ne injection is presented for selected ITER scenarios with the aim of improving our understanding of the physics underlying the runaway heat loads onto the plasma facing components (PFCs) and identifying open issues for developing and accessing disruption mitigation schemes for ITER. This is carried out by means of simplified models, but still retaining sufficient details of the key physical processes, including: (a) the expected dominant runaway generation mechanisms (avalanche and primary runaway seeds: Dreicer and hot tail runaway generation, tritium decay and Compton scattering of γ rays emitted by the activated wall), (b) effects associated with the plasma and runaway current density profile shape, and (c) corrections to the runaway dynamics to account for the collisions of the runaways with the partially stripped impurity ions, which are found to have strong effects leading to low runaway current generation and low energy conversion during current termination for mitigated disruptions by noble gas injection (particularly for Ne injection) for the shortest current quench times compatible with acceptable forces on the ITER vessel and in-vessel components ({τ\\text{res}}∼ 22~\\text{ms} ). For the case of long current quench times ({τ\\text{res}}∼ 66~\\text{ms} ), runaway beams up to  ∼10 MA can be generated during the disruption current quench and, if the termination of the runaway current is slow enough, the generation of runaways by the avalanche mechanism can play an important role, increasing substantially the energy deposited by the runaways onto the PFCs up to a few hundreds of MJs. Mixed impurity (Ar or Ne) plus deuterium injection proves to be effective in controlling the formation of the runaway current during the current quench, even for the longest current quench times, as well as in decreasing

  18. Tidal Disruption Events from Eccentric Nuclear Disks

    Science.gov (United States)

    Wernke, Heather N.; Madigan, Ann-Marie

    2018-04-01

    Stars that get too close to a supermassive black hole are in danger of being tidally disrupted. Stellar two-body relaxation is commonly assumed to be the main driver of these events. Recent work has shown, however, that secular gravitational torques from eccentric nuclear disks can push stars to extreme eccentricities at much higher rates than predicted by two-body relaxation. This work did not include the effects of general relativity, however, which could quench secular torques via rapid apsidal precession. Here we show that, for a star in danger of disruption, general relativity acts on a timescale of less than an orbital period. This short timescale means that general relativity does not have enough time to have a major effect on the orbit. When driven by secular torques from eccentric nuclear disks, tidal disruption event rates are not affected by general relativity.

  19. From Digital Disruption to Business Model Scalability

    DEFF Research Database (Denmark)

    Nielsen, Christian; Lund, Morten; Thomsen, Peter Poulsen

    2017-01-01

    as a response to digital disruption. A series of case studies illustrate that besides frequent existing messages in the business literature relating to the importance of creating agile businesses, both in growing and declining economies, as well as hard to copy value propositions or value propositions that take...... a long time to replicate, business model scalability can be cornered into four dimensions. In many corporate restructuring exercises and Mergers and Acquisitions there is a tendency to look for synergies in the form of cost reductions, lean workflows and market segments. However, this state of mind......This article discusses the terms disruption, digital disruption, business models and business model scalability. It illustrates how managers should be using these terms for the benefit of their business by developing business models capable of achieving exponentially increasing returns to scale...

  20. Density turbulence and disruption phenomena in TEXTOR

    International Nuclear Information System (INIS)

    Waidmann, G.; Kuang, G.; Jadoul, M.

    1992-01-01

    Disruptive processes are observed in tokamak plasmas not only at the operating limits (density limit or q-limit) but can be found under a variety of experimental conditions. Large forces are exerted then on vessel components and support structures. The sudden release of stored plasma energy presents a serious erosion problem for the first wall already in the next generation of large tokamak machines. Strong energy losses from the plasma and an influx of impurities are already present in minor plasma disruptions which do not immediately lead to a plasma current termination. The rapid loss of energy confinement was investigated within the framework of a systematic study on plasma disruption phenomena in TEXTOR. (author) 4 refs., 4 figs

  1. Disruption effects on the beam size measurement

    International Nuclear Information System (INIS)

    Raimondi, P.; Decker, F.J.; Chen, P.

    1995-01-01

    At the SLC Final Focus with higher currents and smaller beam sizes, the disruption parameter D y is close to one and so the pinch effect should produce a luminosity enhancement. Since a flat beam-beam function is fit to deflection scan data to measure the beam size, disruption can affect the measurement. Here the authors discuss the quantitative effects of disruption for typical SLC beam parameters. With 3.5 10 10 particles per pulse, bunch length of 0.8 mm and beam sizes of 2.1 μm horizontally and 0.55 μm vertically, the measured vertical size can be as much as 25% bigger than the real one. Furthermore during the collision the spot size actually decrease, producing an enhancement factor H D of about 1.25. This would yield to a true luminosity which is 1.6 times that which is estimated from the beam-beam deflection fit

  2. Mechanisms of Memory Disruption in Depression.

    Science.gov (United States)

    Dillon, Daniel G; Pizzagalli, Diego A

    2018-03-01

    Depressed individuals typically show poor memory for positive events, potentiated memory for negative events, and impaired recollection. These phenomena are clinically important but poorly understood. Compelling links between stress and depression suggest promising candidate mechanisms. Stress can suppress hippocampal neurogenesis, inhibit dopamine neurons, and sensitize the amygdala. We argue that these phenomena may impair pattern separation, disrupt the encoding of positive experiences, and bias retrieval toward negative events, respectively, thus recapitulating core aspects of memory disruption in depression. Encouragingly, optogenetic reactivation of cells engaged during the encoding of positive memories rapidly reduces depressive behavior in preclinical models. Thus, many memory deficits in depression appear to be downstream consequences of chronic stress, and addressing memory disruption can have therapeutic value. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Isolated Sleep Paralysis: Fear, Prevention, and Disruption.

    Science.gov (United States)

    Sharpless, Brian Andrew; Grom, Jessica Lynn

    2016-01-01

    Relatively little is known about isolated sleep paralysis (ISP), and no empirically supported treatments are available. This study aims to determine: the clinical impact of ISP, the techniques used to prevent or disrupt ISP, and the effectiveness of these techniques. 156 undergraduates were assessed with lifetime ISP using a clinical interview. 75.64% experienced fear during ISP, and 15.38% experienced clinically significant distress/interference, while 19.23% attempted to prevent ISP, and 79.31% of these believed their methods were successful. Regarding disruption, 69.29% made attempts, but only 54.12% reported them effective. Disruption was more common than prevention, but several techniques were useful. Encouraging individuals to utilize these techniques and better monitor their symptoms may be an effective way to manage problematic ISP.

  4. Clothianidin and Imidacloprid Residues in Poa annua (Poales: Poaceae) and Their Effects on Listronotus maculicollis (Coleoptera: Curculionidae).

    Science.gov (United States)

    Clavet, Christopher; Requintina, Matthew; Hampton, Emily; Cowles, Richard S; Byrne, Frank J; Alm, Steven R

    2014-12-01

    Competitive enzyme-linked immunosorbent assay was used to quantify the amounts of the neonicotinoids clothianidin and imidacloprid in Poa annua L. clippings from treated golf course fairways. Average clothianidin residues 7 d after application ranged from 674 to 1,550 ng/g tissue in 2012 and 455-2,220 ng/g tissue in 2013. Average clothianidin residues the day of application ranged from 17,100-38,800 ng/g tissue in 2014. Average imidacloprid residues 7 d after treatment ranged from 1,950-3,030 ng/g tissue in 2012 and 7,780-9,230 ng/g tissue in 2013. Average imidacloprid residues the day of application ranged from 31,500-40,400 ng/g tissue in 2014. Neonicotinoid or bifenthrin-neonicotinoid combination products applied in field plots in 2012 did not significantly reduce the numbers of larvae relative to the untreated control. However, in 2013, statistically significant reductions in the numbers of larvae recovered from treated field plots were associated with the presence of bifenthrin alone or when used in combination with neonicotinoid active ingredients. Listronotus maculicollis (Kirby) adults caged on neonicotinoid-, bifenthrin-, and bifenthrin-neonicotinoid-treated P. annua turf plugs fed on P. annua leaves, but mortality was only highly significantly different between treated and untreated foliage when weevils were placed on treated foliage the day after treatment and allowed to feed for 7 d. The modest degree of population suppression with bifenthrin in these experiments may not be adequate to justify the continued use of these products due to the increased risk of insecticide resistance and disruption of biological control. © 2014 Entomological Society of America.

  5. Analytic modeling of axisymmetric disruption halo currents

    International Nuclear Information System (INIS)

    Humphreys, D.A.; Kellman, A.G.

    1999-01-01

    Currents which can flow in plasma facing components during disruptions pose a challenge to the design of next generation tokamaks. Induced toroidal eddy currents and both induced and conducted poloidal ''halo'' currents can produce design-limiting electromagnetic loads. While induction of toroidal and poloidal currents in passive structures is a well-understood phenomenon, the driving terms and scalings for poloidal currents flowing on open field lines during disruptions are less well established. A model of halo current evolution is presented in which the current is induced in the halo by decay of the plasma current and change in enclosed toroidal flux while being convected into the halo from the core by plasma motion. Fundamental physical processes and scalings are described in a simplified analytic version of the model. The peak axisymmetric halo current is found to depend on halo and core plasma characteristics during the current quench, including machine and plasma dimensions, resistivities, safety factor, and vertical stability growth rate. Two extreme regimes in poloidal halo current amplitude are identified depending on the minimum halo safety factor reached during the disruption. A 'type I' disruption is characterized by a minimum safety factor that remains relatively high (typically 2 - 3, comparable to the predisruption safety factor), and a relatively low poloidal halo current. A 'type II' disruption is characterized by a minimum safety factor comparable to unity and a relatively high poloidal halo current. Model predictions for these two regimes are found to agree well with halo current measurements from vertical displacement event disruptions in DIII-D [T. S. Taylor, K. H. Burrell, D. R. Baker, G. L. Jackson, R. J. La Haye, M. A. Mahdavi, R. Prater, T. C. Simonen, and A. D. Turnbull, open-quotes Results from the DIII-D Scientific Research Program,close quotes in Proceedings of the 17th IAEA Fusion Energy Conference, Yokohama, 1998, to be published in

  6. Disruptive event analysis: volcanism and igneous intrusion

    International Nuclear Information System (INIS)

    Crowe, B.M.

    1980-08-01

    An evaluation is made of the disruptive effects of volcanic activity with respect to long term isolation of radioactive waste through deep geologic storage. Three major questions are considered. First, what is the range of disruption effects of a radioactive waste repository by volcanic activity. Second, is it possible, by selective siting of a repository, to reduce the risk of disruption by future volcanic activity. And third, can the probability of repository disruption by volcanic activity be quantified. The main variables involved in the evaluation of the consequences of repository disruption by volcanic activity are the geometry of the magma-repository intersection (partly controlled by depth of burial) and the nature of volcanism. Potential radionuclide dispersal by volcanic transport within the biosphere ranges in distance from several kilometers to global. Risk from the most catastrophic types of eruptions can be reduced by careful site selection to maximize lag time prior to the onset of activity. Certain areas or volcanic provinces within the western United States have been sites of significant volcanism and should be avoided as potential sites for a radioactive waste repository. Examples of projection of future sites of active volcanism are discussed for three areas of the western United States. Probability calculations require two types of data: a numerical rate or frequency of volcanic activity and a numerical evaluation of the areal extent of volcanic disruption for a designated region. The former is clearly beyond the current state of art in volcanology. The latter can be approximated with a reasonable degree of satisfaction. In this report, simplified probability calculations are attempted for areas of past volcanic activity

  7. Automated selective disruption of slow wave sleep.

    Science.gov (United States)

    Ooms, Sharon J; Zempel, John M; Holtzman, David M; Ju, Yo-El S

    2017-04-01

    Slow wave sleep (SWS) plays an important role in neurophysiologic restoration. Experimentally testing the effect of SWS disruption previously required highly time-intensive and subjective methods. Our goal was to develop an automated and objective protocol to reduce SWS without affecting sleep architecture. We developed a custom Matlab™ protocol to calculate electroencephalogram spectral power every 10s live during a polysomnogram, exclude artifact, and, if measurements met criteria for SWS, deliver increasingly louder tones through earphones. Middle-aged healthy volunteers (n=10) each underwent 2 polysomnograms, one with the SWS disruption protocol and one with sham condition. The SWS disruption protocol reduced SWS compared to sham condition, as measured by spectral power in the delta (0.5-4Hz) band, particularly in the 0.5-2Hz range (mean 20% decrease). A compensatory increase in the proportion of total spectral power in the theta (4-8Hz) and alpha (8-12Hz) bands was seen, but otherwise normal sleep features were preserved. N3 sleep decreased from 20±34 to 3±6min, otherwise there were no significant changes in total sleep time, sleep efficiency, or other macrostructural sleep characteristics. This novel SWS disruption protocol produces specific reductions in delta band power similar to existing methods, but has the advantage of being automated, such that SWS disruption can be performed easily in a highly standardized and operator-independent manner. This automated SWS disruption protocol effectively reduces SWS without impacting overall sleep architecture. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Disruption of the thyroid system by the thyroid-disrupting compound Aroclor 1254 in juvenile Japanese flounder (Paralichthys olivaceus.

    Directory of Open Access Journals (Sweden)

    Yifei Dong

    Full Text Available Polychlorinated biphenyls (PCBs are a group of persistent organochlorine compounds that have the potential to disrupt the homeostasis of thyroid hormones (THs in fish, particularly juveniles. In this study, thyroid histology, plasma TH levels, and iodothyronine deiodinase (IDs, including ID1, ID2, and ID3 gene expression patterns were examined in juvenile Japanese flounder (Paralichthys olivaceus following 25- and 50-day waterborne exposure to environmentally relevant concentrations of a commercial PCB mixture, Aroclor 1254 (10, 100, and 1000 ng/L with two-thirds of the test solutions renewed daily. The results showed that exposure to Aroclor 1254 for 50 d increased follicular cell height, colloid depletion, and hyperplasia. In particular, hypothyroidism, which was induced by the administration of 1000 ng/L Aroclor 1254, significantly decreased plasma TT4, TT3, and FT3 levels. Profiles of the changes in mRNA expression levels of IDs were observed in the liver and kidney after 25 and 50 d PCB exposure, which might be associated with a reduction in plasma THs levels. The expression level of ID2 mRNA in the liver exhibited a dose-dependent increase, indicating that this ID isotype might serve as sensitive and stable indicator for thyroid-disrupting chemical (TDC exposure. Overall, our study confirmed that environmentally relevant concentrations of Aroclor 1254 cause significant thyroid disruption, with juvenile Japanese flounder being suitable candidates for use in TDC studies.

  9. Peer deviance, parenting and disruptive behavior among young girls.

    Science.gov (United States)

    Miller, Shari; Loeber, Rolf; Hipwell, Alison

    2009-02-01

    This study examined concurrent and longitudinal associations between peer deviance, parenting practices, and conduct and oppositional problems among young girls ages 7 and 8. Participants were 588 African American and European American girls who were part of a population-based study of the development of conduct problems and delinquency among girls. Affiliations with problem-prone peers were apparent among a sizeable minority of the girls, and these associations included both males and females. Although peer delinquency concurrently predicted disruptive behaviors, the gender of these peers did not contribute to girls' behavior problems. Harsh parenting and low parental warmth showed both concurrent and prospective associations with girls' disruptive behaviors. Similar patterns of association were seen for African American and European American girls. The findings show that peer and parent risk processes are important contributors to the early development of young girls' conduct and oppositional behaviors. These data contribute to our understanding of girls' aggression and antisocial behaviors and further inform our understanding of risk processes for these behaviors among young girls in particular.

  10. Landfilling of waste incineration residues

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Astrup, Thomas; Cai, Zuansi

    2002-01-01

    Residues from waste incineration are bottom ashes and air-pollution-control (APC) residues including fly ashes. The leaching of heavy metals and salts from the ashes is substantial and a wide spectrum of leaching tests and corresponding criteria have been introduced to regulate the landfilling...

  11. Sedentary behavior and residual-specific mortality

    OpenAIRE

    Paul D. Loprinzi; Meghan K. Edwards; Eveleen Sng; Ovuokerie Addoh

    2016-01-01

    Background: The purpose of this study was to examine the association of accelerometer-assessed sedentary behavior and residual-specific mortality. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5536), with follow-up through 2011. Sedentary behavior was objectively measured over 7 days via accelerometry. Results: When expressing sedentary behavior as a 60 min/day increase, the hazard ratio across the models ranged from 1.07-1.40 (P < 0...

  12. Disruptive Innovation by Emerging Multinational Latecomers

    DEFF Research Database (Denmark)

    Li, Peter Ping

    on disruptive innovation (DI) and the bottom of the pyramid (BOP) provides a great opportunity to shed light on the key issue. To take advantage of this “missed” opportunity, I integrate the two reframed constructs of DI and BOP and also develop a typology of four ideal-typical innovations toward a theory...... of latecomer innovation as a special DI by EMNE at BOP to provide insights into the mechanisms underlying the trajectories of catching up and leapfrogging. Built upon latecomer innovation, EMNEs at BOP can emerge as the most disruptive challengers to the MNE incumbents at TOP. The implications of reframed...

  13. Development of disruption thermal analysis code DREAM

    International Nuclear Information System (INIS)

    Yamazaki, Seiichiro; Kobayahsi, Takeshi; Seki, Masahiro.

    1989-01-01

    When a plasma disruption takes place in a tokamak type fusion reactor, plasma facing componenets such as first wall and divertor/limiter are subjected to a intensse heat load in a short duration. At the surface of the wall, temperature rapidly rises, and melting and evaporation occurs. It causes reduction of wall thickness and crack initiation/propagation. As lifetime of the components is significantly affected by them, the transient analysis in consideration of phase changes and radiation heat loss in required in the design of these components. This paper describes the computer code DREAM, developed to perform the disruption thermal analysis, taking phase changes and radiation into account. (author)

  14. Energetics of LMFBR core disruptive accidents

    International Nuclear Information System (INIS)

    Marchaterre, J.F.

    1979-01-01

    In general, in the design of fast reactor systems, containment design margins are specified by investigating the response of the containment to core disruptive accidents. The results of these analyses are then translated into criteria which the designers must meet. Currently, uniform and agreed upon criteria are lacking, and in this time while they are being developed, the designer should be aware of the considerations which go into the particular criteria he must work with, and participate in their development. This paper gives an overview of the current state of the art in assessing core disruptive accidents and the design implications of this process. (orig.)

  15. Disruptive Technologies and Networking in Telecom Industries

    DEFF Research Database (Denmark)

    Madsen, Erik Strøjer; Hartington, Simon Preuthun

    2015-01-01

    This article discuss’ how economics of scale in supply and demand in the telecommunication industry has developed and how this has had great effect on the widespread usage and popularity of smartphones. By using this as a theoretical ground the paper looks into technical innovation...... in the telecommunication industry and finds significant similarities between the industry development and the literature on disruptive technology, which finds that incumbent companies are not able to react in a successful way when disruptions occur in their industry. By studying how the telecommunication industry...

  16. Disruptive technologies and networking in telecom industries

    DEFF Research Database (Denmark)

    Madsen, Erik Strøjer; Hartington, Simon

    This article discuss’ how economics of scale in supply and demand in the telecommunication industry has developed and how this has had great effect on the widespread usage and popularity of smart phones. By using this as a theoretical ground the paper looks into technical innovation...... in the telecommunication industry and finds significant similarities between the industry development and the literature on disruptive technology, which finds that incumbent companies are not able to react in a successful way when disruptions occur in their industry. By studying how the telecommunication industry...

  17. Statistical inference on residual life

    CERN Document Server

    Jeong, Jong-Hyeon

    2014-01-01

    This is a monograph on the concept of residual life, which is an alternative summary measure of time-to-event data, or survival data. The mean residual life has been used for many years under the name of life expectancy, so it is a natural concept for summarizing survival or reliability data. It is also more interpretable than the popular hazard function, especially for communications between patients and physicians regarding the efficacy of a new drug in the medical field. This book reviews existing statistical methods to infer the residual life distribution. The review and comparison includes existing inference methods for mean and median, or quantile, residual life analysis through medical data examples. The concept of the residual life is also extended to competing risks analysis. The targeted audience includes biostatisticians, graduate students, and PhD (bio)statisticians. Knowledge in survival analysis at an introductory graduate level is advisable prior to reading this book.

  18. Automatic prediction of catalytic residues by modeling residue structural neighborhood

    Directory of Open Access Journals (Sweden)

    Passerini Andrea

    2010-03-01

    Full Text Available Abstract Background Prediction of catalytic residues is a major step in characterizing the function of enzymes. In its simpler formulation, the problem can be cast into a binary classification task at the residue level, by predicting whether the residue is directly involved in the catalytic process. The task is quite hard also when structural information is available, due to the rather wide range of roles a functional residue can play and to the large imbalance between the number of catalytic and non-catalytic residues. Results We developed an effective representation of structural information by modeling spherical regions around candidate residues, and extracting statistics on the properties of their content such as physico-chemical properties, atomic density, flexibility, presence of water molecules. We trained an SVM classifier combining our features with sequence-based information and previously developed 3D features, and compared its performance with the most recent state-of-the-art approaches on different benchmark datasets. We further analyzed the discriminant power of the information provided by the presence of heterogens in the residue neighborhood. Conclusions Our structure-based method achieves consistent improvements on all tested datasets over both sequence-based and structure-based state-of-the-art approaches. Structural neighborhood information is shown to be responsible for such results, and predicting the presence of nearby heterogens seems to be a promising direction for further improvements.

  19. Bisphenol a exposure disrupts genomic imprinting in the mouse.

    Directory of Open Access Journals (Sweden)

    Martha Susiarjo

    2013-04-01

    Full Text Available Exposure to endocrine disruptors is associated with developmental defects. One compound of concern, to which humans are widely exposed, is bisphenol A (BPA. In model organisms, BPA exposure is linked to metabolic disorders, infertility, cancer, and behavior anomalies. Recently, BPA exposure has been linked to DNA methylation changes, indicating that epigenetic mechanisms may be relevant. We investigated effects of exposure on genomic imprinting in the mouse as imprinted genes are regulated by differential DNA methylation and aberrant imprinting disrupts fetal, placental, and postnatal development. Through allele-specific and quantitative real-time PCR analysis, we demonstrated that maternal BPA exposure during late stages of oocyte development and early stages of embryonic development significantly disrupted imprinted gene expression in embryonic day (E 9.5 and 12.5 embryos and placentas. The affected genes included Snrpn, Ube3a, Igf2, Kcnq1ot1, Cdkn1c, and Ascl2; mutations and aberrant regulation of these genes are associated with imprinting disorders in humans. Furthermore, the majority of affected genes were expressed abnormally in the placenta. DNA methylation studies showed that BPA exposure significantly altered the methylation levels of differentially methylated regions (DMRs including the Snrpn imprinting control region (ICR and Igf2 DMR1. Moreover, exposure significantly reduced genome-wide methylation levels in the placenta, but not the embryo. Histological and immunohistochemical examinations revealed that these epigenetic defects were associated with abnormal placental development. In contrast to this early exposure paradigm, exposure outside of the epigenetic reprogramming window did not cause significant imprinting perturbations. Our data suggest that early exposure to common environmental compounds has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the

  20. Childhood family disruption and adult height: is there a mediating role of puberty?

    Science.gov (United States)

    Sheppard, Paula; Garcia, Justin R; Sear, Rebecca

    2015-11-24

    Childhood family background is known to be associated with child growth and development, including the onset of puberty, but less is known about the influence of childhood family disruption on outcomes in later life. Given the associations between early family disruption and childhood development, we predicted that there may be long-term health-relevant consequences of childhood disruption. Using data from a large US interview sample (n = 16 207), we test if death or divorce of parents, at different childhood periods, was associated with adult stature, and whether age at puberty mediated this relationship, for men and women. RESULTS MEN: : parental death and divorce during early childhood was associated with shorter adult height, and later puberty. Later puberty was associated with shorter adult height. Path analyses demonstrated that the relationship between parental divorce and height was completely mediated by age at puberty; although parental death was only partially mediated by age at puberty. WOMEN: the father's death during early childhood was associated with earlier puberty, which was in turn associated with shorter adult stature. The relationship between paternal death and height is entirely mediated by age at puberty; no evidence of a direct relationship between childhood family disruption and adult height. Early childhood familial disruption is associated with shorter height for men, and is partially mediated by later puberty. For women, the relationship between father's death, and height was completely mediated by earlier puberty. These findings indicate that disruption during childhood can have long-reaching health repercussions, particularly for boys. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  1. Critical issues and experimental examination on sawtooth and disruption physics

    International Nuclear Information System (INIS)

    Itoh, K.; Itoh, S.; Fukuyama, A.; Tsuji, S.

    1992-06-01

    The catastrophic phenomena which are associated with the major disruption and sawtooth contain three key processes: (1) Sudden acceleration of the growth of the helical deformation, (2) Central electron temperature crash, and (3) Rearrangement of the plasma current. Based on the theoretical model that the magnetic stochasticity plays a key role in these processes, the critical issues and possible experimental tests are proposed. Present experimental observations would be sufficient to study the detailed sequences and causes. Though models may not be complete the comparison with experiments improves understandings. (author)

  2. Case for integral core-disruptive accident analysis

    International Nuclear Information System (INIS)

    Luck, L.B.; Bell, C.R.

    1985-01-01

    Integral analysis is an approach used at the Los Alamos National Laboratory to cope with the broad multiplicity of accident paths and complex phenomena that characterize the transition phase of core-disruptive accident progression in a liquid-metal-cooled fast breeder reactor. The approach is based on the combination of a reference calculation, which is intended to represent a band of similar accident paths, and associated system- and separate-effect studies, which are designed to determine the effect of uncertainties. Results are interpreted in the context of a probabilistic framework. The approach was applied successfully in two studies; illustrations from the Clinch River Breeder Reactor licensing assessment are included

  3. An Additive-Multiplicative Restricted Mean Residual Life Model

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben; Scheike, Thomas H.

    2016-01-01

    The mean residual life measures the expected remaining life of a subject who has survived up to a particular time. When survival time distribution is highly skewed or heavy tailed, the restricted mean residual life must be considered. In this paper, we propose an additive-multiplicative restricted...... mean residual life model to study the association between the restricted mean residual life function and potential regression covariates in the presence of right censoring. This model extends the proportional mean residual life model using an additive model as its covariate dependent baseline....... For the suggested model, some covariate effects are allowed to be time-varying. To estimate the model parameters, martingale estimating equations are developed, and the large sample properties of the resulting estimators are established. In addition, to assess the adequacy of the model, we investigate a goodness...

  4. Solid residues from Ruminococcus cellulose fermentations as components of wood adhesive formulations

    Science.gov (United States)

    P.J. Weimer; A.H. Conner; L.F. Lorenz

    2003-01-01

    Residues from the fermentation of cellulose by the anaerobic bacteria Ruminococcus albus (strain 7) or Ruminococcus flavefaciens (strains FD-1 or B34b) containing residual cellulose, bacterial cells and their associated adhesins, were examined for their ability to serve as components of adhesives for plywood fabrication. The residues contained differing amounts of...

  5. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. Grøne; Krægpøth, Morten; Nielsen, Helena Skyt

    This paper estimates how peers’ achievement gains are affected by the presence of potentially disruptive and emotionally sensitive children in the school-cohort. We exploit that some children move between schools and thus generate variation in peer composition in the receiving school-cohort. We i...

  6. Naval sonar disrupts foraging in humpback whales

    NARCIS (Netherlands)

    Sivle, L.D.; Wensveen, P.J.; Kvadsheim, P.H.; Lam, F.P.A.; Visser, F.; Curé, C.; Harris, C.M.; Tyack, P.L.; Miller, P.J.O.

    2016-01-01

    Modern long-range naval sonars are a potential disturbance for marine mammals and can cause disruption of feeding in cetaceans. We examined the lunge-feeding behaviour of humpback whales Megaptera novaeangliae before, during and after controlled exposure experiments with naval sonar by use of

  7. Disruptive Innovation by Emerging Multinational Latecomers

    DEFF Research Database (Denmark)

    Li, Peter Ping

    on disruptive innovation (DI) and the bottom of the pyramid (BOP) provides a great opportunity to shed light on the key issue. To take advantage of this “missed” opportunity, I integrate the two reframed constructs of DI and BOP and also develop a typology of four ideal-typical innovations toward a theory...

  8. Biosensor discovery of thyroxine transport disrupting chemicals

    NARCIS (Netherlands)

    Marchesini, G.R.; Meimaridou, A.; Haasnoot, W.; Meulenberg, E.; Albertus, F.; Mizuguchi, M.; Takeuchi, M.; Irth, H.; Murk, A.J.

    2008-01-01

    Ubiquitous chemicals may interfere with the thyroid system that is essential in the development and physiology of vertebrates. We applied a surface plasmon resonance (SPR) biosensor-based screening method for the fast screening of chemicals with thyroxine (T4) transport disrupting activity. Two

  9. Gender, Career Disruption, and Academic Rewards.

    Science.gov (United States)

    McElrath, Karen

    1992-01-01

    A survey of 314 male and female faculty in criminology and sociology found that faculty women are more likely than men to leave academic positions, and women who interrupt careers commonly do so for a job-seeking spouse. Women experience significant losses in tenure and earnings as a result of career disruptions. (MSE)

  10. Is Online Learning a Disruptive Innovation?

    Science.gov (United States)

    Meyer, Katrina A.

    2011-01-01

    In their desire to plan for the future, planners must assess the role of both internal and external influences on the institution. What then should people make of the idea that technology is disruptive? This perception fuels the views of Barone and Hagner (2001), who claimed that technology would "transform" higher education; Duderstadt (2000),…

  11. Management of posterior urethral disruption injuries.

    Science.gov (United States)

    Myers, Jeremy B; McAninch, Jack W

    2009-03-01

    Posterior urethral disruption is a traumatic injury to the male urethra, which most often results from pelvic fracture. After trauma, the distraction defect between the two ends of the urethra often scars and becomes fibrotic, blocking the urethra and bladder emptying. Increasing evidence suggests that many posterior urethral disruptions occur at the junction between the membranous urethra and the bulbar urethra, which is distal to the rhabdosphincter. In the acute setting, when a posterior urethral disruption is suspected, retrograde urethrography should be performed. Posterior urethral disruptions can be managed acutely by realignment of the urethra over a urethral catheter or by placement of a suprapubic catheter for bladder drainage only. Once fibrosis has stabilized, the patient can undergo posterior urethroplasty. In most cases, this procedure can be performed via a perineal approach in a single-stage surgery. The results of this single-stage perineal urethroplasty are excellent, and a patent urethra can be re-established in the majority of men who undergo surgery.

  12. Histopathological and biochemical disrupting effects of Escravos ...

    African Journals Online (AJOL)

    user

    2014-02-27

    Feb 27, 2014 ... The aim of this study was to investigate the histological and biochemical disrupting effects of Escravos ... rupturing or leaking of production infrastructures that are described as, “very old and lack regular ... crude oil were measured in weight on an electronic weighing balance and given orally (oral gavage) ...

  13. Disrupted functional connectivity in adolescent obesity

    Directory of Open Access Journals (Sweden)

    Laura Moreno-Lopez

    2016-01-01

    Conclusions: These findings suggest that adolescent obesity is linked to disrupted functional connectivity in brain networks relevant to maintaining balance between reward, emotional memories and cognitive control. Our findings may contribute to reconceptualization of obesity as a multi-layered brain disorder leading to compromised motivation and control, and provide a biological account to target prevention strategies for adolescent obesity.

  14. Disrupting Educational Inequalities through Youth Digital Activism

    Science.gov (United States)

    Stornaiuolo, Amy; Thomas, Ebony Elizabeth

    2017-01-01

    This article reviews scholarship on youth and young adult activism in digital spaces, as young users of participatory media sites are engaging in political, civic, social, or cultural action and advocacy online to create social change. The authors argue that youth's digital activism serves as a central mechanism to disrupt inequality, and that…

  15. Natural and Professional Help during Marital Disruption.

    Science.gov (United States)

    Toro, Paul A.; Zax, Melvin

    Although few people bring their psychological problems to mental health professionals, research in the area of 'natural' help is rudimentary. To investigate the process and effectiveness of natural professional groups in helping individuals experiencing marital disruption, 42 helpers (14 mental health professionals, 14 divorce lawyers, and 14…

  16. Dynamics and radiation from tidal disruption events

    NARCIS (Netherlands)

    Bonnerot, C.A.

    2017-01-01

    When a star gets too close to a supermassive black hole, it is torn apart by strong tidal forces in a tidal disruption event (TDE). The stellar matter then fuels the compact object causing a bright flare that is a unique probe of the majority of galactic nuclei, otherwise quiescent. For

  17. Heavy Metals Acting as Endocrine Disrupters

    Directory of Open Access Journals (Sweden)

    Bogdan Georgescu

    2011-10-01

    Full Text Available Last years researches focused on several natural and synthetic compounds that may interfere with the major functionsof the endocrine system and were termed endocrine disrupters. Endocrine disrupters are defined as chemicalsubstances with either agonist or antagonist endocrine effects in human and animals. These effects may be achievedby interferences with the biosynthesis or activity of several endogenous hormones. Recently, it was demonstratedthat heavy metals such as cadmium (Cd, arsen (As, mercury (Hg, nickel (Ni, lead (Pb and zinc (Zn may exhibitendocrine-disrupting activity in animal experiments. Emerging evidence of the intimate mechanisms of action ofthese heavy metals is accumulating. It was revealed, for example, that the Zn atom from the Zn fingers of theestrogen receptor can be replaced by several heavy metal molecules such as copper, cobalt, Ni and Cd. By replacingthe Zn atom with Ni or copper, binding of the estrogen receptor to the DNA hormone responsive elements in the cellnucleus is prevented. In both males and females, low-level exposure to Cd interferes with the biological effects ofsteroid hormones in reproductive organs. Arsen has the property to bind to the glucocorticoid receptor thusdisturbing glucocorticoids biological effects. With regard to Hg, this may induce alterations in male and femalefertility, may affect the function of the hypothalamo-pituitary-thyroid axis or the hypothalamo-pituitary-adrenal axis,and disrupt biosynthesis of steroid hormones.

  18. Preliminary investigation into the possible endocrine disrupting ...

    African Journals Online (AJOL)

    JTEkanem

    Preliminary investigation into the possible endocrine disrupting activity of Bonny light crude oil contaminated - diet on ... rats (twenty male and twenty five females) were expose to Bonny –light crude oil contaminated diet at concentrations of 1%, 5% and 10% .... also being implicated in possessing antiestrogenic activity9.

  19. Time scales in tidal disruption events

    Directory of Open Access Journals (Sweden)

    Krolik J.

    2012-12-01

    Full Text Available We explore the temporal structure of tidal disruption events pointing out the corresponding transitions in the lightcurves of the thermal accretion disk and of the jet emerging from such events. The hydrodynamic time scale of the disrupted star is the minimal time scale of building up the accretion disk and the jet and it sets a limit on the rise time. This suggest that Swift J1644+57, that shows several flares with a rise time as short as a few hundred seconds could not have arisen from a tidal disruption of a main sequence star whose hydrodynamic time is a few hours. The disrupted object must have been a white dwarf. A second important time scale is the Eddington time in which the accretion rate changes form super to sub Eddington. It is possible that such a transition was observed in the light curve of Swift J2058+05. If correct this provides interesting constraints on the parameters of the system.

  20. The Relative Ineffectiveness of Criminal Network Disruption

    Science.gov (United States)

    Duijn, Paul A. C.; Kashirin, Victor; Sloot, Peter M. A.

    2014-01-01

    Researchers, policymakers and law enforcement agencies across the globe struggle to find effective strategies to control criminal networks. The effectiveness of disruption strategies is known to depend on both network topology and network resilience. However, as these criminal networks operate in secrecy, data-driven knowledge concerning the effectiveness of different criminal network