WorldWideScience

Sample records for rapidly disrupts immunity

  1. Extinction order and altered community structure rapidly disrupt ecosystem functioning.

    Science.gov (United States)

    Larsen, Trond H; Williams, Neal M; Kremen, Claire

    2005-05-01

    By causing extinctions and altering community structure, anthropogenic disturbances can disrupt processes that maintain ecosystem integrity. However, the relationship between community structure and ecosystem functioning in natural systems is poorly understood. Here we show that habitat loss appeared to disrupt ecosystem functioning by affecting extinction order, species richness and abundance. We studied pollination by bees in a mosaic of agricultural and natural habitats in California and dung burial by dung beetles on recently created islands in Venezuela. We found that large-bodied bee and beetle species tended to be both most extinction-prone and most functionally efficient, contributing to rapid functional loss. Simulations confirmed that extinction order led to greater disruption of function than predicted by random species loss. Total abundance declined with richness and also appeared to contribute to loss of function. We demonstrate conceptually and empirically how the non-random response of communities to disturbance can have unexpectedly large functional consequences.

  2. Beneficial Autoimmunity at Body Surfaces – Immune Surveillance and Rapid Type 2 Immunity Regulate Tissue Homeostasis and Cancer

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis. PMID:25101088

  3. Beneficial autoimmunity at body surfaces - immune surveillance and rapid type 2 immunity regulate tissue homeostasis and cancer.

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress - a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis.

  4. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Science.gov (United States)

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

  5. Smooth and Controlled Recovery Planning of Disruptions in Rapid Transit Networks

    NARCIS (Netherlands)

    Cadarso, L.; Marin, A.; Maroti, G.

    2015-01-01

    This paper studies the disruption management problem of rapid transit rail networks. We consider an integrated model for the recovery of the timetable and the rolling stock schedules. We propose a new approach to deal with large-scale disruptions: we limit the number of simultaneous schedule changes

  6. The application of automatic chemiluminescence machine in rapid immune detection

    International Nuclear Information System (INIS)

    Lin Aizhen; Li Xuanwei; Chen Binhong; Li Zhenqian; Chen Zhaoxuan

    2004-01-01

    Objective: To provide high-quality, rapid and dependable result for clinical practice, and give satisfactory service to patients of different economical status by supplementation with other labeling immune examination. With an innovative attitude, we carried out efficient technical reform on ACS180 automatic chemiluminescence machine, making it possible for patients to complete the whole process including examination, check-out, diagnosis and getting drugs. The reported will be issued within an hour, thus a rapid immune detection service was established in out-patients department. Methods: 1. ACS-180 automatic chemiluminescence machine is used based on the principle of chemiluminescence immune methods. 2. The reagents are provided by Ciba-Comig Company of USA, composed of anti acridinium ester antibody of liquid phase and particulate antigen of solid phase wrapped in magnetic powder. 3. Calibration and quality control: high and low concentration are set for each calibration fluid with attached standard curve. Product for quality controlling includes three concentration of low, moderate and high. Results: 1. rapid machine detection for sample: serum is replaced with plasma coagulated by heparin, and comparison among series of methods using serum or plasma suggest no significant difference exists. 2. The problem about fasting detection: chemiluminescence machine measure optical density directly, with the results hardly being influenced by turbidity. But attention should be paid to the treatment of lipid turbid samples. 3. Other innovations: (1) direct placement of sample tube on machine: a cushion is placed on sample plate to transfer sample to machine directly after centrifugation, saving time and reducing the accident in sample transference. (2) for HCG quantification in blood and urine, 'gold criteria' is used firstly in screening to determine approximately the dilution range, with an advantage of saving time and reagent as well as accuracy. (3) we design a

  7. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

    Science.gov (United States)

    Davenport, A J; Cross, R S; Watson, K A; Liao, Y; Shi, W; Prince, H M; Beavis, P A; Trapani, J A; Kershaw, M H; Ritchie, D S; Darcy, P K; Neeson, P J; Jenkins, M R

    2018-02-27

    Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. Copyright © 2018 the Author(s). Published by PNAS.

  8. Disrupted rapid eye movement sleep predicts poor declarative memory performance in post-traumatic stress disorder.

    Science.gov (United States)

    Lipinska, Malgorzata; Timol, Ridwana; Kaminer, Debra; Thomas, Kevin G F

    2014-06-01

    Successful memory consolidation during sleep depends on healthy slow-wave and rapid eye movement sleep, and on successful transition across sleep stages. In post-traumatic stress disorder, sleep is disrupted and memory is impaired, but relations between these two variables in the psychiatric condition remain unexplored. We examined whether disrupted sleep, and consequent disrupted memory consolidation, is a mechanism underlying declarative memory deficits in post-traumatic stress disorder. We recruited three matched groups of participants: post-traumatic stress disorder (n = 16); trauma-exposed non-post-traumatic stress disorder (n = 15); and healthy control (n = 14). They completed memory tasks before and after 8 h of sleep. We measured sleep variables using sleep-adapted electroencephalography. Post-traumatic stress disorder-diagnosed participants experienced significantly less sleep efficiency and rapid eye movement sleep percentage, and experienced more awakenings and wake percentage in the second half of the night than did participants in the other two groups. After sleep, post-traumatic stress disorder-diagnosed participants retained significantly less information on a declarative memory task than controls. Rapid eye movement percentage, wake percentage and sleep efficiency correlated with retention of information over the night. Furthermore, lower rapid eye movement percentage predicted poorer retention in post-traumatic stress disorder-diagnosed individuals. Our results suggest that declarative memory consolidation is disrupted during sleep in post-traumatic stress disorder. These data are consistent with theories suggesting that sleep benefits memory consolidation via predictable neurobiological mechanisms, and that rapid eye movement disruption is more than a symptom of post-traumatic stress disorder. © 2014 European Sleep Research Society.

  9. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-01-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

  10. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  11. 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...

  12. Rapid, portable detection of endocrine disrupting chemicals through ligand-nuclear hormone receptor interactions.

    Science.gov (United States)

    Hunt, J Porter; Schinn, Song-Min; Jones, Matthew D; Bundy, Bradley C

    2017-12-04

    Endocrine disrupting chemicals (EDC) are structurally diverse compounds that can interact with nuclear hormone receptors, posing significant risk to human and ecological health. Unfortunately, many conventional biosensors have been too structure-specific, labor-intensive or laboratory-oriented to detect broad ranges of EDC effectively. Recently, several technological advances are providing more rapid, portable, and affordable detection of endocrine-disrupting activity through ligand-nuclear hormone receptor interactions. Here, we overview these recent advances applied to EDC biosensors - including cell lyophilization, cell immobilization, cell-free systems, smartphone-based signal detection, and improved competitive binding assays.

  13. Effect of skin barrier disruption on immune responses to topically applied cross-reacting material, CRM(197), of diphtheria toxin.

    Science.gov (United States)

    Godefroy, S; Peyre, M; Garcia, N; Muller, S; Sesardic, D; Partidos, C D

    2005-08-01

    The high accessibility of the skin and the presence of immunocompetent cells in the epidermis makes this surface an attractive route for needle-free administration of vaccines. However, the lining of the skin by the stratum corneum is a major obstacle to vaccine delivery. In this study we examined the effect of skin barrier disruption on the immune responses to the cross-reacting material CRM(197), a nontoxic mutant of diphtheria toxin (DTx) that is considered as a vaccine candidate. Application of CRM(197), together with cholera toxin (CT), onto the tape-stripped skin of mice elicited antibody responses that had anti-DTx neutralizing activity. Vaccine delivery onto mildly ablated skin or intact skin did not elicit any detectable anti-CRM(197) antibodies. Mice immunized with CRM(197) alone onto the tape-stripped skin mounted a vigorous antigen-specific proliferative response. In contrast, the induction of cellular immunity after CRM(197) deposition onto mildly ablated or intact skin was adjuvant dependent. Furthermore, epidermal cells were activated and underwent apoptosis that was more pronounced when the stratum corneum was removed by tape stripping. Overall, these findings highlight the potential for transcutaneous delivery of CRM(197) and establish a correlation between the degree of barrier disruption and levels of antigen-specific immune responses. Moreover, these results provide the first evidence that the development of a transcutaneous immunization strategy for diphtheria, based on simple and practical methods to disrupt the skin barrier, is feasible.

  14. Participation of hypothalamic CB1 receptors in reproductive axis disruption during immune challenge.

    Science.gov (United States)

    Surkin, P N; Di Rosso, M E; Correa, F; Elverdin, J C; Genaro, A M; De Laurentiis, A; Fernández-Solari, J

    2017-08-01

    Immune challenge inhibits reproductive function and endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the eCB system mediates the inhibition of hormones that control reproduction as a result of immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on the hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated i.c.v. administration with a CB1 antagonist/inverse agonist (AM251) (500 ng/5 μL), followed by an i.p. injection of lipopolysaccharide (LPS) (5 mg/kg) 15 minutes later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 minutes post-LPS. The plasma concentration of tumour necrosis factor α and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 180 minutes post i.p. administration of LPS. However, cytokine mRNA expression in the hypothalamus increased only 180 minutes post-LPS, suggesting an inflammatory delay in this organ. CB1 receptor blockade with AM251 increased LPS inflammatory effects, particularly in the hypothalamus. LPS also inhibited the HPG axis by decreasing gonadotrophin-releasing hormone hypothalamic content and plasma levels of luteinising hormone and testosterone. These disruptor effects were accompanied by decreased hypothalamic Kiss1 mRNA expression and prostaglandin E2 content, as well as by increased gonadotrophin-inhibitory hormone (Rfrp3) mRNA expression. All these disruptive effects were prevented by the presence of AM251. In summary, our results suggest that, in male rats, eCB mediate immune challenge-inhibitory effects on reproductive axis at least partially via hypothalamic CB1 activation. In addition, this receptor also participates in homeostasis recovery by modulating the inflammatory process taking place after LPS

  15. Alzheimer’s disease Aβ assemblies mediating rapid disruption of synaptic plasticity and memory

    Directory of Open Access Journals (Sweden)

    Klyubin Igor

    2012-07-01

    Full Text Available Abstract Alzheimer’s disease (AD is characterized by episodic memory impairment that often precedes clinical diagnosis by many years. Probing the mechanisms of such impairment may provide much needed means of diagnosis and therapeutic intervention at an early, pre-dementia, stage. Prior to the onset of significant neurodegeneration, the structural and functional integrity of synapses in mnemonic circuitry is severely compromised in the presence of amyloidosis. This review examines recent evidence evaluating the role of amyloid-ß protein (Aβ in causing rapid disruption of synaptic plasticity and memory impairment. We evaluate the relative importance of different sizes and conformations of Aβ, including monomer, oligomer, protofibril and fibril. We pay particular attention to recent controversies over the relevance to the pathophysiology of AD of different water soluble Aβ aggregates and the importance of cellular prion protein in mediating their effects. Current data are consistent with the view that both low-n oligomers and larger soluble assemblies present in AD brain, some of them via a direct interaction with cellular prion protein, cause synaptic memory failure. At the two extremes of aggregation, monomers and fibrils appear to act in vivo both as sources and sinks of certain metastable conformations of soluble aggregates that powerfully disrupt synaptic plasticity. The same principle appears to apply to other synaptotoxic amyloidogenic proteins including tau, α-synuclein and prion protein.

  16. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis

    Science.gov (United States)

    Millet, Arnaud; Martin, Katherine R.; Bonnefoy, Francis; Saas, Philippe; Mocek, Julie; Alkan, Manal; Terrier, Benjamin; Kerstein, Anja; Tamassia, Nicola; Satyanarayanan, Senthil Kumaran; Ariel, Amiram; Ribeil, Jean-Antoine; Guillevin, Loïc; Cassatella, Marco A.; Mueller, Antje; Thieblemont, Nathalie; Lamprecht, Peter; Mouthon, Luc; Perruche, Sylvain; Witko-Sarsat, Véronique

    2015-01-01

    Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology. PMID:26436651

  17. Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence

    Directory of Open Access Journals (Sweden)

    María J. Navarro-Arias

    2016-12-01

    Full Text Available The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of the PMR1 homolog in a low-virulent species that rarely causes candidiasis, Candida guilliermondii. We disrupted C. guilliermondii PMR1 and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite there was a significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicate C. guilliermondii sensing by monocytes was critically dependent on the recognition of N-linked mannans and β1,3-glucan, as reported in other Candida species. In addition, chemical remotion of cell wall O-linked mannans was found to positively influence the recognition of C. guilliermondii by human monocytes, suggesting that O-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported in C. albicans. Finally, mice infected with C. guilliermondii pmr1 null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in the Galleria mellonella infection model. This study thus demonstrates that mannans are relevant for the C. guilliermondii-host interaction, with

  18. Rapid Assay of Cellular Immunity in Q Fever.

    Science.gov (United States)

    1995-10-01

    measuring CMI Measurement of CMI has been accomplished by many different methods both in vitro and in vivo (Clough & Roth , 1995). Some methods are...also become chronic with endocarditis as the main symptom and can result in death. Vaccines are being developed and have shown encouraging success in...rickettsial diseases with strong cellular immune responses following infection. The efficacy of a vaccine against Rocky Mountain spotted fever, R

  19. The habitat disruption induces immune-suppression and oxidative stress in honey bees

    Science.gov (United States)

    Morimoto, Tomomi; Kojima, Yuriko; Toki, Taku; Komeda, Yayoi; Yoshiyama, Mikio; Kimura, Kiyoshi; Nirasawa, Keijiro; Kadowaki, Tatsuhiko

    2011-01-01

    The honey bee is a major insect used for pollination of many commercial crops worldwide. Although the use of honey bees for pollination can disrupt the habitat, the effects on their physiology have never been determined. Recently, honey bee colonies have often collapsed when introduced in greenhouses for pollination in Japan. Thus, suppressing colony collapses and maintaining the number of worker bees in the colonies is essential for successful long-term pollination in greenhouses and recycling of honey bee colonies. To understand the physiological states of honey bees used for long-term pollination in greenhouses, we characterized their gene expression profiles by microarray. We found that the greenhouse environment changes the gene expression profiles and induces immune-suppression and oxidative stress in honey bees. In fact, the increase of the number of Nosema microsporidia and protein carbonyl content was observed in honey bees during pollination in greenhouses. Thus, honey bee colonies are likely to collapse during pollination in greenhouses when heavily infested with pathogens. Degradation of honey bee habitat by changing the outside environment of the colony, during pollination services for example, imposes negative impacts on honey bees. Thus, worldwide use of honey bees for crop pollination in general could be one of reasons for the decline of managed honey bee colonies. PMID:22393496

  20. Mechanical disruption of tumors by iron particles and magnetic field application results in increased anti-tumor immune responses.

    Directory of Open Access Journals (Sweden)

    Myriam N Bouchlaka

    Full Text Available The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread. This treatment was associated with increased activation of DCs in the draining lymph nodes and recruitment of both DCs and CD8(+T cells to the tumor. The particles remained within the tumor and no toxicities were observed. The immune induction observed was significantly greater compared to cryoablation. Further anti-tumor effects were observed when MRF/magnet therapy was combined with systemic low dose immunotherapy. Thus, mechanical disruption of the primary tumor with MRF/magnetic field application represents a novel means to induce systemic immune activation in cancer.

  1. Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory.

    Science.gov (United States)

    Varga, Andrew W; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P; Osorio, Ricardo S; Rapoport, David M; Ayappa, Indu

    2014-10-29

    Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. Copyright © 2014 the authors 0270-6474/14/3414571-07$15.00/0.

  2. Mobile Technology in the Perioperative Arena: Rapid Evolution and Future Disruption.

    Science.gov (United States)

    Rothman, Brian S; Gupta, Rajnish K; McEvoy, Matthew D

    2017-03-01

    Throughout the history of medicine, physicians have relied upon disruptive innovations and technologies to improve the quality of care delivered, patient outcomes, and patient satisfaction. The implementation of mobile technology in health care is quickly becoming the next disruptive technology. We first review the history of mobile technology over the past 3 decades, discuss the impact of hardware and software, explore the rapid expansion of applications (apps), and evaluate the adoption of mobile technology in health care. Next, we discuss how technology serves as the vehicle that can transform traditional didactic learning into one that adapts to the learning behavior of the student by using concepts such as the flipped classroom, just-in-time learning, social media, and Web 2.0/3.0. The focus in this modern education paradigm is shifting from teacher-centric to learner-centric, including providers and patients, and is being delivered as context-sensitive, or semantic, learning. Finally, we present the methods by which connected health systems via mobile devices increase information collection and analysis from patients in both clinical care and research environments. This enhanced patient and provider connection has demonstrated benefits including reducing unnecessary hospital readmissions, improved perioperative health maintenance coordination, and improved care in remote and underserved areas. A significant portion of the future of health care, and specifically perioperative medicine, revolves around mobile technology, nimble learners, patient-specific information and decision-making, and continuous connectivity between patients and health care systems. As such, an understanding of developing or evaluating mobile technology likely will be important for anesthesiologists, particularly with an ever-expanding scope of practice in perioperative medicine.

  3. An overview of estrogen-associated endocrine disruption in fishes: evidence of effects on reproductive and immune physiology

    Science.gov (United States)

    Iwanowicz, L.R.; Blazer, V.S.

    2011-01-01

    Simply and perhaps intuitively defined, endocrine disruption is the abnormal modulation of normal hormonal physiology by exogenous chemicals. In fish, endocrine disruption of the reproductive system has been observed worldwide in numerous species and is known to affect both males and females. Observations of biologically relevant endocrine disruption most commonly occurs near waste water treatment plant outfalls, pulp and paper mills, and areas of high organic loading sometimes associated with agricultural practices. Estrogenic endocrine disrupting chemicals (EEDCs) have received an overwhelmingly disproportionate amount of scientific attention compared to other EDCs in recent years. In male fishes, exposure to EEDCs can lead to the induction of testicular oocytes (intersex), measurable plasma vitellogenin protein, altered sex steroid profiles, abnormal spawning behavior, skewed population sex ratios, and lessened reproductive success. Interestingly, contemporary research purports that EDCs modulate aspects of non-reproductive physiology including immune function. Here we present an overview of endocrine disruption in fishes associated with estrogenic compounds, implications of this phenomenon, and examples of EDC related research findings by our group in the Potomac River Watershed, USA.

  4. The impact of shift work induced chronic circadian disruption on IL-6 and TNF-α immune responses

    Directory of Open Access Journals (Sweden)

    Spallek Michael

    2010-07-01

    Full Text Available Abstract AIM Sleep disturbances induce proinflammatory immune responses, which might increase cardiovascular disease risk. So far the effects of acute sleep deprivation and chronic sleep illnesses on the immune system have been investigated. The particular impact of shift work induced chronic circadian disruption on specific immune responses has not been addressed so far. Methods Pittsburgh-Sleep-Quality-Index (PSQI questionnaire and blood sampling was performed by 225 shift workers and 137 daytime workers. As possible markers the proinflammatory cytokines IL-6 and TNF-α and lymphocyte cell count were investigated. A medical examination was performed and biometrical data including age, gender, height, weight, waist and hip circumference and smoking habits were collected by a structured interview. Results Shift workers had a significantly higher mean PSQI score than day workers (6.73 vs. 4.66; p Conclusion Shift work induces chronic sleep debt. Our data reveals that chronic sleep debt might not always lead to an activation of the immune system, as we did not observe differences in lymphocyte count or level of IL-6 or TNF-α serum concentration between shift workers and day workers. Therefore chronic sleep restriction might be eased by a long-term compensating immune regulation which (in healthy protects against an overstimulation of proinflammatory immune mechanisms and moderates metabolic changes, as they are known from short-term sleep deprivation or sleep related breathing disorders.

  5. Simulated bacterial infection disrupts the circadian fluctuation of immune cells in wrinkle-lipped bats (Chaerephon plicatus

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    Philipp Weise

    2017-08-01

    Full Text Available Background Leukocyte concentrations follow a circadian pattern in mammals, with elevated values at times of potential contact with pathogens and parasites. We hypothesized that this pattern is disturbed after an immune challenge. Methods In Thailand, we captured wrinkle-lipped bats (Chaerephon plicatus, when they returned to their colony at dawn. We challenged half of the animals (experimental group with bacterial lipopolysaccharides and treated the others only with the carrier liquid (control group. We then compared body mass changes and differences in circulating immune cell counts at 8 h post-treatment. Results In experimental animals, we observed an increase in total leukocyte and neutrophil numbers of 17% and 95%, respectively. In control animals, concentrations of leukocytes decreased by 44% and those of neutrophils remained constant. Experimental treatment had no effect on lymphocytes, yet changes in eosinophil numbers were explained by sex. Eosinophils decreased by 66% in females and by 62% in males. Basophils and monocytes were rarest among all observed cell types and analysis was either impossible because of low numbers or yielded no significant effects, respectively. Discussion Our findings show that a simulated bacterial infection triggered a neutrophil-associated immune response in wrinkle-lipped bats, indicating a disruption of the diurnal fluctuation of immune cells. Our study suggests that bats exhibit circadian rhythms in immune cell counts. The magnitude of these fluctuations may vary across species according to specific-specific infection risks associated with colony sizes or specific roosting habits.

  6. Rapid Extraction of Genomic DNA from Medically Important Yeasts and Filamentous Fungi by High-Speed Cell Disruption

    OpenAIRE

    Müller, Frank-Michael C.; Werner, Katherine E.; Kasai, Miki; Francesconi, Andrea; Chanock, Stephen J.; Walsh, Thomas J.

    1998-01-01

    Current methods of DNA extraction from different fungal pathogens are often time-consuming and require the use of toxic chemicals. DNA isolation from some fungal organisms is difficult due to cell walls or capsules that are not readily susceptible to lysis. We therefore investigated a new and rapid DNA isolation method using high-speed cell disruption (HSCD) incorporating chaotropic reagents and lysing matrices in comparison to standard phenol-chloroform (PC) extraction protocols for isolatio...

  7. Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria.

    Directory of Open Access Journals (Sweden)

    Damián Pérez-Mazliah

    2015-03-01

    Full Text Available Interleukin-21 signaling is important for germinal center B-cell responses, isotype switching and generation of memory B cells. However, a role for IL-21 in antibody-mediated protection against pathogens has not been demonstrated. Here we show that IL-21 is produced by T follicular helper cells and co-expressed with IFN-γ during an erythrocytic-stage malaria infection of Plasmodium chabaudi in mice. Mice deficient either in IL-21 or the IL-21 receptor fail to resolve the chronic phase of P. chabaudi infection and P. yoelii infection resulting in sustained high parasitemias, and are not immune to re-infection. This is associated with abrogated P. chabaudi-specific IgG responses, including memory B cells. Mixed bone marrow chimeric mice, with T cells carrying a targeted disruption of the Il21 gene, or B cells with a targeted disruption of the Il21r gene, demonstrate that IL-21 from T cells signaling through the IL-21 receptor on B cells is necessary to control chronic P. chabaudi infection. Our data uncover a mechanism by which CD4+ T cells and B cells control parasitemia during chronic erythrocytic-stage malaria through a single gene, Il21, and demonstrate the importance of this cytokine in the control of pathogens by humoral immune responses. These data are highly pertinent for designing malaria vaccines requiring long-lasting protective B-cell responses.

  8. Innate lymphoid cells: models of plasticity for immune homeostasis and rapid responsiveness in protection.

    Science.gov (United States)

    Almeida, F F; Belz, G T

    2016-09-01

    Innate lymphoid cells (ILCs) have stormed onto the immune landscape as "newly discovered" cell types. These tissue-resident sentinels are enriched at mucosal surfaces and engage in complex cross talk with elements of the adaptive immune system and microenvironment to orchestrate immune homeostasis. Many parallels exist between innate cells and T cells leading to the initial partitioning of ILCs into rather rigid subsets that reflect their "adaptive-like" effector cytokines profiles. ILCs themselves, however, have unique attributes that are only just beginning to be elucidated. These features result in complementarity with, rather than complete duplication of, functions of the adaptive immune system. Key transcription factors determine the pathway of differentiation of progenitors towards an ILC1, ILC2, or ILC3 subset. Once formed, flexibility in the responses of these subsets to stimuli unexpectedly allows transdifferentation between the different subsets and the acquisition of altered phenotypes and function. This provides a mechanism for rapid innate immune responsiveness. Here, we discuss the models of differentiation for maintenance and activation of tissue-resident ILCs in maintaining immune homeostasis and protection.

  9. New Clox Systems for rapid and efficient gene disruption in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Shahida Shahana

    Full Text Available Precise genome modification is essential for the molecular dissection of Candida albicans, and is yielding invaluable information about the roles of specific gene functions in this major fungal pathogen of humans. C. albicans is naturally diploid, unable to undergo meiosis, and utilizes a non-canonical genetic code. Hence, specialized tools have had to be developed for gene disruption in C. albicans that permit the deletion of both target alleles, and in some cases, the recycling of the Candida-specific selectable markers. Previously, we developed a tool based on the Cre recombinase, which recycles markers in C. albicans with 90-100% efficiency via site-specific recombination between loxP sites. Ironically, the utility of this system was hampered by the extreme efficiency of Cre, which prevented the construction in Escherichia coli of stable disruption cassettes carrying a methionine-regulatable CaMET3p-cre gene flanked by loxP sites. Therefore, we have significantly enhanced this system by engineering new Clox cassettes that carry a synthetic, intron-containing cre gene. The Clox kit facilitates efficient transformation and marker recycling, thereby simplifying and accelerating the process of gene disruption in C. albicans. Indeed, homozygous mutants can be generated and their markers resolved within two weeks. The Clox kit facilitates strategies involving single marker recycling or multi-marker gene disruption. Furthermore, it includes the dominant NAT1 marker, as well as URA3, HIS1 and ARG4 cassettes, thereby permitting the manipulation of clinical isolates as well as genetically marked strains of C. albicans. The accelerated gene disruption strategies afforded by this new Clox system are likely to have a profound impact on the speed with which C. albicans pathobiology can be dissected.

  10. The habitat disruption induces immune-suppression and oxidative stress in honey bees

    OpenAIRE

    Morimoto, Tomomi; Kojima, Yuriko; Toki, Taku; Komeda, Yayoi; Yoshiyama, Mikio; Kimura, Kiyoshi; Nirasawa, Keijiro; Kadowaki, Tatsuhiko

    2011-01-01

    The honey bee is a major insect used for pollination of many commercial crops worldwide. Although the use of honey bees for pollination can disrupt the habitat, the effects on their physiology have never been determined. Recently, honey bee colonies have often collapsed when introduced in greenhouses for pollination in Japan. Thus, suppressing colony collapses and maintaining the number of worker bees in the colonies is essential for successful long-term pollination in greenhouses and recycli...

  11. A bacterial E3 ubiquitin ligase targets a host protein kinase to disrupt plant immunity.

    Science.gov (United States)

    Rosebrock, Tracy R; Zeng, Lirong; Brady, Jennifer J; Abramovitch, Robert B; Xiao, Fangming; Martin, Gregory B

    2007-07-19

    Many bacterial pathogens of plants and animals use a type III secretion system to deliver diverse virulence-associated 'effector' proteins into the host cell. The mechanisms by which these effectors act are mostly unknown; however, they often promote disease by suppressing host immunity. One type III effector, AvrPtoB, expressed by the plant pathogen Pseudomonas syringae pv. tomato, has a carboxy-terminal domain that is an E3 ubiquitin ligase. Deletion of this domain allows an amino-terminal region of AvrPtoB (AvrPtoB(1-387)) to be detected by certain tomato varieties leading to immunity-associated programmed cell death. Here we show that a host kinase, Fen, physically interacts with AvrPtoB(1-387 )and is responsible for activating the plant immune response. The AvrPtoB E3 ligase specifically ubiquitinates Fen and promotes its degradation in a proteasome-dependent manner. This degradation leads to disease susceptibility in Fen-expressing tomato lines. Various wild species of tomato were found to exhibit immunity in response to AvrPtoB(1-387 )and not to full-length AvrPtoB. Thus, by acquiring an E3 ligase domain, AvrPtoB has thwarted a highly conserved host resistance mechanism.

  12. The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in immunity

    Energy Technology Data Exchange (ETDEWEB)

    Buoso, Erica; Galasso, Marilisa; Ronfani, Melania [Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia (Italy); Papale, Angela; Galbiati, Valentina [Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano (Italy); Eberini, Ivano [Laboratorio di Biochimica e Biofisica Computazionale, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan (Italy); Marinovich, Marina [Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano (Italy); Racchi, Marco [Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia (Italy); Corsini, Emanuela, E-mail: emanuela.corsini@unimi.it [Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano (Italy)

    2017-06-15

    We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p′DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p′DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity and protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p′DDT and p,p′DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p′DDE exerting a stronger repressor effect than p,p′DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system. - Highlights: • RACK1 expression can be induced by AR agonists with a consequent enhancement of the response to LPS. • RACK1 can be negatively modulated by the AR antagonists DDT and its main metabolite p,p′DDE. • RACK1 can be a relevant target of EDCs, representing a bridge between the endocrine system and the immune system.

  13. Rapid changes in the light/dark cycle disrupt memory of conditioned fear in mice.

    Directory of Open Access Journals (Sweden)

    Dawn H Loh

    Full Text Available BACKGROUND: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/dark (LD cycle. Such "jet lag" treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. METHODOLOGY/PRINCIPAL FINDINGS: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. CONCLUSIONS/SIGNIFICANCE: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that a synchronized circadian system may be broadly important for normal cognition and that the consolidation of memories may be particularly sensitive to disruptions of circadian timing.

  14. Ocular surface immunity: homeostatic mechanisms and their disruption in dry eye disease.

    Science.gov (United States)

    Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

    2012-05-01

    The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Rapid analysis for 567 pesticides and endocrine disrupters by GC/MS using deconvolution reporting software

    Energy Technology Data Exchange (ETDEWEB)

    Wylie, P.; Szelewski, M.; Meng, Chin-Kai [Agilent Technologies, Wilmington, DE (United States)

    2004-09-15

    More than 700 pesticides are approved for use around the world, many of which are suspected endocrine disrupters. Other pesticides, though no longer used, persist in the environment where they bioaccumulate in the flora and fauna. Analytical methods target only a subset of the possible compounds. The analysis of food and environmental samples for pesticides is usually complicated by the presence of co-extracted natural products. Food or tissue extracts can be exceedingly complex matrices that require several stages of sample cleanup prior to analysis. Even then, it can be difficult to detect trace levels of contaminants in the presence of the remaining matrix. For efficiency, multi-residue methods (MRMs) must be used to analyze for most pesticides. Traditionally, these methods have relied upon gas chromatography (GC) with a constellation of element-selective detectors to locate pesticides in the midst of a variable matrix. GC with mass spectral detection (GC/MS) has been widely used for confirmation of hits. Liquid chromatography (LC) has been used for those compounds that are not amenable to GC. Today, more and more pesticide laboratories are relying upon LC with mass spectral detection (LC/MS) and GC/MS as their primary analytical tools. Still, most MRMs are target compound methods that look for a small subset of the possible pesticides. Any compound not on the target list is likely to be missed by these methods. Using the techniques of retention time locking (RTL) and RTL database searching together with spectral deconvolution, a method has been developed to screen for 567 pesticides and suspected endocrine disrupters in a single GC/MS analysis. Spectral deconvolution helps to identify pesticides even when they co-elute with matrix compounds while RTL helps to eliminate false positives and gives greater confidence in the results.

  16. Rapid extraction of genomic DNA from medically important yeasts and filamentous fungi by high-speed cell disruption.

    Science.gov (United States)

    Müller, F M; Werner, K E; Kasai, M; Francesconi, A; Chanock, S J; Walsh, T J

    1998-06-01

    Current methods of DNA extraction from different fungal pathogens are often time-consuming and require the use of toxic chemicals. DNA isolation from some fungal organisms is difficult due to cell walls or capsules that are not readily susceptible to lysis. We therefore investigated a new and rapid DNA isolation method using high-speed cell disruption (HSCD) incorporating chaotropic reagents and lysing matrices in comparison to standard phenol-chloroform (PC) extraction protocols for isolation of DNA from three medically important yeasts (Candida albicans, Cryptococcus neoformans, and Trichosporon beigelii) and two filamentous fungi (Aspergillus fumigatus and Fusarium solani). Additional extractions by HSCD were performed on Saccharomyces cerevisiae, Pseudallescheria boydii, and Rhizopus arrhizus. Two different inocula (10(8) and 10(7) CFU) were compared for optimization of obtained yields. The entire extraction procedure was performed on as many as 12 samples within 1 h compared to 6 h for PC extraction. In comparison to the PC procedure, HSCD DNA extraction demonstrated significantly greater yields for 10(8) CFU of C. albicans, T. beigelii, A. fumigatus, and F. solani (P extraction and PC extraction. For 10(7) CFU of T. beigelii, PC extraction resulted in a greater yield than did HSCD (P fungi than for yeasts by the HSCD extraction procedure (P extraction procedure, differences were not significant. For all eight organisms, the rapid extraction procedure resulted in good yield, integrity, and quality of DNA as demonstrated by restriction fragment length polymorphism, PCR, and random amplified polymorphic DNA. We conclude that mechanical disruption of fungal cells by HSCD is a safe, rapid, and efficient procedure for extracting genomic DNA from medically important yeasts and especially from filamentous fungi.

  17. Towards an integrated biosensor array for simultaneous and rapid multi-analysis of endocrine disrupting chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Scognamiglio, Viviana, E-mail: viviana.scognamiglio@mlib.ic.cnr.it [IC-CNR Istituto di Cristallografia, AdR1 Dipartimento Agroalimentare - Via Salaria Km 29.3 00015, Rome (Italy); Pezzotti, Italo; Pezzotti, Gianni; Cano, Juan; Manfredonia, Ivano [Biosensor S.r.l. - Via degli Olmetti 44 00060 Formello, Rome (Italy); Buonasera, Katia [IC-CNR Istituto di Cristallografia, AdR1 Dipartimento Agroalimentare - Via Salaria Km 29.3 00015, Rome (Italy); Arduini, Fabiana; Moscone, Danila; Palleschi, Giuseppe [Universita di Roma Tor Vergata, Dipartimento di Scienze e Tecnologie Chimiche - Via della Ricerca Scientifica 00133, Rome (Italy); Giardi, Maria Teresa [IC-CNR Istituto di Cristallografia, AdR1 Dipartimento Agroalimentare - Via Salaria Km 29.3 00015, Rome (Italy)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer A multitask biosensor for the detection of endocrine disrupting chemicals is proposed. Black-Right-Pointing-Pointer The sensing system employ an array of biological recognition elements. Black-Right-Pointing-Pointer Amperometric and optical transduction methods are provided in an integrated biosensor together with flow control systems. Black-Right-Pointing-Pointer The biosensing device results in an integrated, automatic and portable system for environmental and agrifood application. - Abstract: In this paper we propose the construction and application of a portable multi-purpose biosensor array for the simultaneous detection of a wide range of endocrine disruptor chemicals (EDCs), based on the recognition operated by various enzymes and microorganisms. The developed biosensor combines both electrochemical and optical transduction systems, in order to increase the number of chemical species which can be monitored. Considering to the maximum residue level (MRL) of contaminants established by the European Commission, the biosensor system was able to detect most of the chemicals analysed with very high sensitivity. In particular, atrazine and diuron were detected with a limit of detection of 0.5 nM, with an RSD% less than 5%; paraoxon and chlorpyrifos were revealed with a detection of 5 {mu}M and 4.5 {mu}M, respectively, with an RSD% less than 6%; catechol and bisphenol A were identified with a limit of detection of 1 {mu}M and 35 {mu}M respectively, with an RSD% less than 5%.

  18. Towards an integrated biosensor array for simultaneous and rapid multi-analysis of endocrine disrupting chemicals

    International Nuclear Information System (INIS)

    Scognamiglio, Viviana; Pezzotti, Italo; Pezzotti, Gianni; Cano, Juan; Manfredonia, Ivano; Buonasera, Katia; Arduini, Fabiana; Moscone, Danila; Palleschi, Giuseppe; Giardi, Maria Teresa

    2012-01-01

    Highlights: ► A multitask biosensor for the detection of endocrine disrupting chemicals is proposed. ► The sensing system employ an array of biological recognition elements. ► Amperometric and optical transduction methods are provided in an integrated biosensor together with flow control systems. ► The biosensing device results in an integrated, automatic and portable system for environmental and agrifood application. - Abstract: In this paper we propose the construction and application of a portable multi-purpose biosensor array for the simultaneous detection of a wide range of endocrine disruptor chemicals (EDCs), based on the recognition operated by various enzymes and microorganisms. The developed biosensor combines both electrochemical and optical transduction systems, in order to increase the number of chemical species which can be monitored. Considering to the maximum residue level (MRL) of contaminants established by the European Commission, the biosensor system was able to detect most of the chemicals analysed with very high sensitivity. In particular, atrazine and diuron were detected with a limit of detection of 0.5 nM, with an RSD% less than 5%; paraoxon and chlorpyrifos were revealed with a detection of 5 μM and 4.5 μM, respectively, with an RSD% less than 6%; catechol and bisphenol A were identified with a limit of detection of 1 μM and 35 μM respectively, with an RSD% less than 5%.

  19. SPRYSEC effectors: a versatile protein-binding platform to disrupt plant innate immunity

    Directory of Open Access Journals (Sweden)

    Amalia Diaz-Granados

    2016-10-01

    Full Text Available Persistent infections by sedentary plant-parasitic nematodes are a major threat to important food crops all over the world. These round worms manipulate host plant cell morphology and physiology to establish sophisticated feeding structures. Key modifications to plant cells during their transition into feeding structures are largely attributed to the activity of effectors secreted by the nematodes. The SPRYSEC effectors were initially identified in the potato cyst nematodes Globodera rostochiensis and G. pallida, and are characterized by a single SPRY domain, a non-catalytic domain present in modular proteins with different functions. The SPRY domain is wide-spread among eukaryotes and thought to be involved in mediating protein-protein interactions. Thus far, the SPRY domain is only reported as a functional domain in effectors of plant-parasitic nematodes, but not of other plant pathogens. SPRYSEC effectors have been implicated in both suppression and activation of plant immunity, but other possible roles in nematode virulence remain undefined. Here, we review the latest reports on the structure, function, and sequence diversity of SPRYSEC effectors, which provide support for a model featuring these effectors as a versatile protein-binding platform for the nematodes to target a wide range of host proteins during parasitism.

  20. Rapid eye movement sleep deprivation disrupts consolidation but not reconsolidation of novel object recognition memory in rats.

    Science.gov (United States)

    Chen, Lin; Tian, Shaowen; Ke, Jie

    2014-03-20

    There is increasing evidence that sleep plays a critical role in memory consolidation. However, there are comparatively few studies that have assessed the relationship between sleep and memory reconsolidation. In the present study, we explored the effects of rapid eye movement sleep deprivation (RSD) on the consolidation (experiment 1) and reconsolidation (experiment 2) of novel object recognition memory in rats. In experiment 1 behavioral procedure involved two training phases: sample and test. Rats were subjected to 6h RSD starting either immediately after sample (exposed to 2 objects) or 6h later. In experiment 2 behavioral procedure involved three training phases: sample, reactivation and test. Rats were subjected to 6h RSD starting either immediately after reactivation (exposed to the same 2 sample objects to reactivate the memory trace) or 6h later. Results from experiment 1 showed that post-sample RSD from 0 to 6h but not 6 to 12h disrupted novel object recognition memory consolidation. However, we found that post-reactivation RSD whether from 0 to 6h or 6 to 12h had no effect on novel object recognition memory reconsolidation in experiment 2. The results indicated that RSD selectively disrupted consolidation of novel object recognition memory, suggesting a dissociation effect of RSD on consolidation and reconsolidation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    Science.gov (United States)

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  2. High contaminant loads in Lake Apopka's riparian wetland disrupt gene networks involved in reproduction and immune function in largemouth bass.

    Science.gov (United States)

    Martyniuk, Christopher J; Doperalski, Nicholas J; Prucha, Melinda S; Zhang, Ji-Liang; Kroll, Kevin J; Conrow, Roxanne; Barber, David S; Denslow, Nancy D

    2016-09-01

    Lake Apopka (FL, USA) has elevated levels of some organochlorine pesticides in its sediments and a portion of its watershed has been designated a US Environmental Protection Agency Superfund site. This study assessed reproductive endpoints in Florida largemouth bass (LMB) (Micropterus salmoides floridanus) after placement into experimental ponds adjacent to Lake Apopka. LMB collected from a clean reference site (DeLeon Springs) were stocked at two periods of time into ponds constructed in former farm fields on the north shore of the lake. LMB were stocked during early and late oogenesis to determine if there were different effects of contamination on LMB that may be attributed to their reproductive stage. LMB inhabiting the ponds for ~4months had anywhere from 2 to 800 times higher contaminant load for a number of organochlorine pesticides (e.g. p, p'-DDE, methoxychlor) compared to control animals. Gonadosomatic index and plasma vitellogenin were not different between reproductively-stage matched LMB collected at reference sites compared to those inhabiting the ponds. However, plasma 17β-estradiol was lower in LMB inhabiting the Apopka ponds compared to ovary stage-matched LMB from the St. Johns River, a site used as a reference site. Sub-network enrichment analysis revealed that genes related to reproduction (granulosa function, oocyte development), endocrine function (steroid metabolism, hormone biosynthesis), and immune function (T cell suppression, leukocyte accumulation) were differentially expressed in the ovaries of LMB placed into the ponds. These data suggest that (1) LMB inhabiting the Apopka ponds showed disrupted reproduction and immune responses and that (2) gene expression profiles provided site-specific information by discriminating LMB from different macro-habitats. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Detection of immunotoxic effects of estrogenic and androgenic endocrine disrupting compounds using splenic immune cells of the female three-spined stickleback, Gasterosteus aculeatus (L.).

    Science.gov (United States)

    Bado-Nilles, A; Techer, R; Porcher, J M; Geffard, A; Gagnaire, B; Betoulle, S; Sanchez, W

    2014-09-01

    Today, the list of endocrine disrupting compounds (EDCs) in freshwater and marine environments that mimic or block endogenous hormones is expanding at an alarming rate. As immune and reproductive systems may interact in a bidirectional way, some authors proposed the immune capacities as attractive markers to evaluate the hormonal potential of environmental samples. Thus, the present work proposed to gain more knowledge on direct biological effects of natural and EDCs on female fish splenic leucocyte non-specific immune activities by using ex vivo assays. After determining the optimal required conditions to analyze splenic immune responses, seven different EDCs were tested ex vivo at 0.01, 1 and 100nM over 12h on the leucocyte functions of female three-spined stickleback, Gasterosteus aculeatus. In summary, we found that natural hormones acted as immunostimulants, whilst EDCs were immunosuppressive. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Rapid identification of genes controlling virulence and immunity in malaria parasites

    KAUST Repository

    Abkallo, Hussein M.

    2017-07-13

    Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

  5. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  6. Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

    Science.gov (United States)

    Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

    2015-10-27

    The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of

  7. A Simple and Rapid Gene Disruption Strategy in Mycobacterium abscessus: On the Design and Application of Glycopeptidolipid Mutants.

    Science.gov (United States)

    Viljoen, Albertus; Gutiérrez, Ana Victoria; Dupont, Christian; Ghigo, Eric; Kremer, Laurent

    2018-01-01

    Little is known about the disease-causing genetic determinants that are used by Mycobacterium abscessus , increasingly acknowledged as an important emerging pathogen, notably in cystic fibrosis. The presence or absence of surface exposed glycopeptidolipids (GPL) conditions the smooth (S) or rough (R) M. abscessus subsp. abscessus ( M. abscessus ) variants, respectively, which are characterized by distinct infective programs. However, only a handful of successful gene knock-out and conditional mutants have been reported in M. abscessus , testifying that genetic manipulation of this mycobacterium is difficult. To facilitate gene disruption and generation of conditional mutants in M. abscessus , we have designed a one-step single cross-over system that allows the rapid and simple generation of such mutants. Cloning of as small as 300 bp of the target gene allows for efficient homologous recombination to occur without additional exogenous recombination-promoting factors. The presence of tdTomato on the plasmids allows easily sifting out the large background of mutants spontaneously resistant to antibiotics. Using this strategy in the S genetic background and the target gene mmpL4a , necessary for GPL synthesis and transport, nearly 100% of red fluorescent clones exhibited a rough morphotype and lost GPL on the surface, suggesting that most red fluorescent colonies obtained after transformation incorporated the plasmid through homologous recombination into the chromosome. This system was further exploited to generate another strain with reduced GPL levels to explore how the presence of these cell wall-associated glycolipids influences M. abscessus hydrophobicity as well as virulence in the zebrafish model of infection. This mutant exhibited a more pronounced killing phenotype in zebrafish embryos compared to its S progenitor and this effect correlated with the production of abscesses in the central nervous system. Overall, these results suggest that the near

  8. RAPID APPRAISAL OF ROUTINE IMMUNIZATION COVERAGE IN A NEWLY FORMED DISTRICT OF UTTAR PRADESH

    Directory of Open Access Journals (Sweden)

    S K Kaushal

    2011-12-01

    Full Text Available Background Immunization is a proven cost effective intervention to reduce the child mortality & morbidity. As per DLHS-3(2007-08 only 30.3% of children are fully immunized in Uttar Pradesh. A new district, Kanshi Ram Nagar was created on 15 April 2008 within Etah district. Objective To assess the primary immunization status & dropout rate. To find out reasons for immunization default. To study the difference, if any between high risk & low risk block. Material & methods A cross sectional, observational study was undertaken in two blocks (Patiyali and Amanpur of Kanshi Ram Nagar District by interviewing 210 respondent mothers in each block, by using ‘30’ cluster sampling technique with help of predesigned, pretested schedule. Result: The percentages of fully immunized children were 50% in Patiyali & 44.08% in Amanpur block. ANM & ASHA were observed as main informer to the community. Immunization status was poor in Muslims and in female children. The highest covered antigen found was BCG and lowest was DPT-3 in both the blocks. The overall dropout rate was 36.52% for Patiyali & 32.96 % for Amanpur block. The main reasons for dropout identified were, non-cooperation of health workers and community were not aware about the need of Immunization in both the blocks. However the differential findings in among the blocks were statistically not significant. Conclusion However lesser number of children were left untouched for immunization services but the percentage of incomplete immunization was found high due to poor cooperation of health worker and unawareness about need of immunization in community

  9. Development of a high-throughput microscale cell disruption platform for Pichia pastoris in rapid bioprocess design.

    Science.gov (United States)

    Bláha, Benjamin A F; Morris, Stephen A; Ogonah, Olotu W; Maucourant, Sophie; Crescente, Vincenzo; Rosenberg, William; Mukhopadhyay, Tarit K

    2018-01-01

    The time and cost benefits of miniaturized fermentation platforms can only be gained by employing complementary techniques facilitating high-throughput at small sample volumes. Microbial cell disruption is a major bottleneck in experimental throughput and is often restricted to large processing volumes. Moreover, for rigid yeast species, such as Pichia pastoris, no effective high-throughput disruption methods exist. The development of an automated, miniaturized, high-throughput, noncontact, scalable platform based on adaptive focused acoustics (AFA) to disrupt P. pastoris and recover intracellular heterologous protein is described. Augmented modes of AFA were established by investigating vessel designs and a novel enzymatic pretreatment step. Three different modes of AFA were studied and compared to the performance high-pressure homogenization. For each of these modes of cell disruption, response models were developed to account for five different performance criteria. Using multiple responses not only demonstrated that different operating parameters are required for different response optima, with highest product purity requiring suboptimal values for other criteria, but also allowed for AFA-based methods to mimic large-scale homogenization processes. These results demonstrate that AFA-mediated cell disruption can be used for a wide range of applications including buffer development, strain selection, fermentation process development, and whole bioprocess integration. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:130-140, 2018. © 2017 American Institute of Chemical Engineers.

  10. Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oglionucleotides

    National Research Council Canada - National Science Library

    Klinman, Dennise

    2001-01-01

    This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

  11. Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oligonucleotides

    National Research Council Canada - National Science Library

    Klinman, Dennis

    2003-01-01

    This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory "CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

  12. Rapid Induction of Protective Immunity Against Biothreat Agens Using CPG-Based Oglionucleotides

    National Research Council Canada - National Science Library

    Klinman, Dennis

    1999-01-01

    This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG' motifs to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

  13. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available Anti-tumor necrosis factor alpha (anti-TNF-α therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  14. A Force-Activated Trip Switch Triggers Rapid Dissociation of a Colicin from Its Immunity Protein

    Science.gov (United States)

    Farrance, Oliver E.; Hann, Eleanore; Kaminska, Renata; Housden, Nicholas G.; Derrington, Sasha R.; Kleanthous, Colin; Radford, Sheena E.; Brockwell, David J.

    2013-01-01

    Colicins are protein antibiotics synthesised by Escherichia coli strains to target and kill related bacteria. To prevent host suicide, colicins are inactivated by binding to immunity proteins. Despite their high avidity (Kd≈fM, lifetime ≈4 days), immunity protein release is a pre-requisite of colicin intoxication, which occurs on a timescale of minutes. Here, by measuring the dynamic force spectrum of the dissociation of the DNase domain of colicin E9 (E9) and immunity protein 9 (Im9) complex using an atomic force microscope we show that application of low forces (force-triggered increase in off-rate a trip bond. Using mutational analysis, we elucidate the mechanism of this switch in affinity. We show that the N-terminal region of E9, which has sparse contacts with the hydrophobic core, is linked to an allosteric activator region in E9 (residues 21–30) whose remodelling triggers immunity protein release. Diversion of the force transduction pathway by the introduction of appropriately positioned disulfide bridges yields a force resistant complex with a lifetime identical to that measured by ensemble techniques. A trip switch within E9 is ideal for its function as it allows bipartite complex affinity, whereby the stable colicin:immunity protein complex required for host protection can be readily converted to a kinetically unstable complex whose dissociation is necessary for cellular invasion and competitor death. More generally, the observation of two force phenotypes for the E9:Im9 complex demonstrates that force can re-sculpt the underlying energy landscape, providing new opportunities to modulate biological reactions in vivo; this rationalises the commonly observed discrepancy between off-rates measured by dynamic force spectroscopy and ensemble methods. PMID:23431269

  15. High-risk Long QT Syndrome Mutations in the Kv7.1 (KCNQ1) Pore Disrupt the Molecular Basis for Rapid K+ Permeation

    Science.gov (United States)

    Burgess, Don E.; Bartos, Daniel C.; Reloj, Allison R.; Campbell, Kenneth S.; Johnson, Jonathan N.; Tester, David J.; Ackerman, Michael J.; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Delisle, Brian P.

    2012-01-01

    Type 1 long QT syndrome (LQT1) syndrome is caused by loss-of-function mutations in the KCNQ1, which encodes the K+ channel (Kv7.1) that underlies the slowly activating delayed rectifier K+ current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss-of-function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confer a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated non-functional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamic simulations (MDS) of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K+-K+ repulsive forces required for rapid K+ permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K+ channel selectivity filter. PMID:23092362

  16. High-risk long QT syndrome mutations in the Kv7.1 (KCNQ1) pore disrupt the molecular basis for rapid K(+) permeation.

    Science.gov (United States)

    Burgess, Don E; Bartos, Daniel C; Reloj, Allison R; Campbell, Kenneth S; Johnson, Jonathan N; Tester, David J; Ackerman, Michael J; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J; Ohno, Seiko; Horie, Minoru; Delisle, Brian P

    2012-11-13

    Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1 gene, which encodes the K(+) channel (Kv7.1) that underlies the slowly activating delayed rectifier K(+) current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss of function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confers a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated nonfunctional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamics simulations of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K(+)-K(+) repulsive forces required for rapid K(+) permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K(+) channel selectivity filter.

  17. Rapid identification of genes controlling virulence and immunity in malaria parasites

    KAUST Repository

    Abkallo, Hussein M.; Martinelli, Axel; Inoue, Megumi; Ramaprasad, Abhinay; Xangsayarath, Phonepadith; Gitaka, Jesse; Tang, Jianxia; Yahata, Kazuhide; Zoungrana, Augustin; Mitaka, Hayato; Acharjee, Arita; Datta, Partha P.; Hunt, Paul; Carter, Richard; Kaneko, Osamu; Mustonen, Ville; Illingworth, Christopher J. R.; Pain, Arnab; Culleton, Richard

    2017-01-01

    Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic

  18. Granzyme B Disrupts Central Metabolism and Protein Synthesis in Bacteria to Promote an Immune Cell Death Program.

    Science.gov (United States)

    Dotiwala, Farokh; Sen Santara, Sumit; Binker-Cosen, Andres Ariel; Li, Bo; Chandrasekaran, Sriram; Lieberman, Judy

    2017-11-16

    Human cytotoxic lymphocytes kill intracellular microbes. The cytotoxic granule granzyme proteases released by cytotoxic lymphocytes trigger oxidative bacterial death by disrupting electron transport, generating superoxide anion and inactivating bacterial oxidative defenses. However, they also cause non-oxidative cell death because anaerobic bacteria are also killed. Here, we use differential proteomics to identify granzyme B substrates in three unrelated bacteria: Escherichia coli, Listeria monocytogenes, and Mycobacteria tuberculosis. Granzyme B cleaves a highly conserved set of proteins in all three bacteria, which function in vital biosynthetic and metabolic pathways that are critical for bacterial survival under diverse environmental conditions. Key proteins required for protein synthesis, folding, and degradation are also substrates, including multiple aminoacyl tRNA synthetases, ribosomal proteins, protein chaperones, and the Clp system. Because killer cells use a multipronged strategy to target vital pathways, bacteria may not easily become resistant to killer cell attack. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Disrupted PI3K p110δ Signaling Dysregulates Maternal Immune Cells and Increases Fetal Mortality In Mice

    Directory of Open Access Journals (Sweden)

    Jens Kieckbusch

    2015-12-01

    Full Text Available Maternal immune cells are an integral part of reproduction, but how they might cause pregnancy complications remains elusive. Macrophages and their dual function in inflammation and tissue repair are thought to play key yet undefined roles. Altered perinatal growth underpins adult morbidity, and natural killer (NK cells may sustain fetal growth by establishing the placental blood supply. Using a mouse model of genetic inactivation of PI3K p110δ, a key intracellular signaling molecule in leukocytes, we show that p110δ regulates macrophage dynamics and NK-cell-mediated arterial remodeling. The uterus of dams with inactive p110δ had decreased IFN-γ and MHC class IIlow macrophages but enhanced IL-6. Poor vascular remodeling and a pro-inflammatory uterine milieu resulted in fetal death or growth retardation. Our results provide one mechanism that explains how imbalanced adaptations of maternal innate immune cells to gestation affect offspring well-being with consequence perinatally and possibly into adulthood.

  20. Rapid emergence of free-riding behavior in new pediatric immunization programs.

    Directory of Open Access Journals (Sweden)

    Chris T Bauch

    Full Text Available BACKGROUND: Mathematical models have formalized how free-rider effects can threaten the stability of high vaccine coverage levels under established voluntary vaccination programs. However, little research has addressed the question of when free-riding begins to develop when a new vaccine is first introduced in a population. METHODOLOGY/PRINCIPAL FINDINGS: Here, we combine a game theoretical model of vaccinating behavior with an age-structured compartmental model to analyze rational vaccinating behavior in the first years of a universal immunization program, where a new vaccine is free to all children of a specified age. The model captures how successive birth cohorts face different epidemiological landscapes that have been shaped by the vaccinating decisions of previous birth cohorts, resulting in a strategic interaction between individuals in different birth cohorts. The model predicts a Nash equilibrium coverage level of for the first few birth cohorts under the new program. However, free-riding behavior emerges very quickly, with the Nash equilibrium vaccine coverage dropping significantly within 2-5 years after program initiation. Subsequently, a rich set of coupled dynamics between infection prevalence and vaccinating behaviors is possible, ranging from relatively stable (but reduced coverage in later birth cohorts to wide fluctuations in vaccine coverage from one birth cohort to the next. Individual tolerance for vaccine risk also starts out at relatively high levels before dropping significantly within a few years. CONCLUSIONS/SIGNIFICANCE: These results suggest that even relatively new immunization programs can be vulnerable to drops in vaccine coverage caused by vaccine scares and exacerbated by herd immunity effects, necessitating vigilance from the start.

  1. Novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (Orf virus genome

    Directory of Open Access Journals (Sweden)

    McGuire Michael J

    2012-01-01

    Full Text Available Abstract Background The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach. Results The genome of Parapoxvirus ovis (Orf virus was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer. Conclusion A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration

  2. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood.

    Science.gov (United States)

    Schaafsma, Wandert; Basterra, Laura Bozal; Jacobs, Sabrina; Brouwer, Nieske; Meerlo, Peter; Schaafsma, Anne; Boddeke, Erik W G M; Eggen, Bart J L

    2017-10-01

    Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia, the innate immune cells of the central nervous system (CNS). In mice, a challenge with LPS during late gestation stages (days 15-16-17) induced a pro-inflammatory response in fetal microglia. Adult whole brain microglia of mice that were exposed to LPS during embryonic development displayed a persistent reduction in pro-inflammatory activation in response to a re-challenge with LPS. In contrast, hippocampal microglia of these mice displayed an increased inflammatory response to an LPS re-challenge. In addition, a reduced expression of brain-derived neurotrophic factor (BDNF) was observed in hippocampal microglia of LPS-offspring. Microglia-derived BDNF has been shown to be important for learning and memory processes. In line with these observations, behavioral- and learning tasks with mice that were exposed to maternal inflammation revealed reduced home cage activity, reduced anxiety and reduced learning performance in a T-maze. These data show that exposure to maternal inflammation during late gestation results in long term changes in microglia responsiveness during adulthood, which is different in nature in hippocampus compared to total brain microglia. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Transcriptional networks associated with the immune system are disrupted by organochlorine pesticides in largemouth bass (Micropterus salmoides) ovary.

    Science.gov (United States)

    Martyniuk, Christopher J; Doperalski, Nicholas J; Feswick, April; Prucha, Melinda S; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2016-08-01

    were altered by p, p' DDE, MXC, and flutamide. Interestingly, immune-related gene networks were suppressed by all three chemicals. The data suggest that p, p' DDE and flutamide affected more genes in common with each other than either chemical with MXC, consistent with studies suggesting that p, p' DDE is a more potent anti-androgen than MXC. These data demonstrate that reproductive health was not affected by these specific dietary treatments, but rather the immune system, which may be a significant target of organochlorine pesticides. The interaction between the reproductive and immune systems should be considered in future studies on these legacy and persistent pesticides. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Rapid and sustained CD4(+) T-cell-independent immunity from adenovirus-encoded vaccine antigens

    DEFF Research Database (Denmark)

    Holst, Peter J; Bartholdy, Christina; Buus, Anette Stryhn

    2007-01-01

    -linked lymphocytic choriomeningitis virus (LCMV)-derived epitopes was long-lived and protective. Notably, in contrast to full-length protein, the response elicited with the beta(2)-microglobulin-linked LCMV-derived epitope was CD4(+) T-cell independent. Furthermore, virus-specific CD8(+) T cells primed...... in the absence of CD4(+) T-cell help were sustained in the long term and able to expand and control a secondary challenge with LCMV. Our results demonstrate that modifications to the antigen used in adenovirus vaccines may be used to improve the induced T-cell response. Such a strategy for CD4(+) T-cell...... to that elicited with an adenovirus-encoded minimal epitope covalently linked to beta(2)-microglobulin. We demonstrate that the beta(2)-microglobulin-linked epitope induced an accelerated and augmented CD8(+) T-cell response. Furthermore, the immunity conferred by vaccination with beta(2)-microglobulin...

  5. Disruption of the novel gene fad104 causes rapid postnatal death and attenuation of cell proliferation, adhesion, spreading and migration

    International Nuclear Information System (INIS)

    Nishizuka, Makoto; Kishimoto, Keishi; Kato, Ayumi; Ikawa, Masahito; Okabe, Masaru; Sato, Ryuichiro; Niida, Hiroyuki; Nakanishi, Makoto; Osada, Shigehiro; Imagawa, Masayoshi

    2009-01-01

    The molecular mechanisms at the beginning of adipogenesis remain unknown. Previously, we identified a novel gene, fad104 (factor for adipocyte differentiation 104), transiently expressed at the early stage of adipocyte differentiation. Since the knockdown of the expression of fad104 dramatically repressed adipogenesis, it is clear that fad104 plays important roles in adipocyte differentiation. However, the physiological roles of fad104 are still unknown. In this study, we generated fad104-deficient mice by gene targeting. Although the mice were born in the expected Mendelian ratios, all died within 1 day of birth, suggesting fad104 to be crucial for survival after birth. Furthermore, analyses of mouse embryonic fibroblasts (MEFs) prepared from fad104-deficient mice provided new insights into the functions of fad104. Disruption of fad104 inhibited adipocyte differentiation and cell proliferation. In addition, cell adhesion and wound healing assays using fad104-deficient MEFs revealed that loss of fad104 expression caused a reduction in stress fiber formation, and notably delayed cell adhesion, spreading and migration. These results indicate that fad104 is essential for the survival of newborns just after birth and important for cell proliferation, adhesion, spreading and migration

  6. Ex vivo cytosolic delivery of functional macromolecules to immune cells.

    Directory of Open Access Journals (Sweden)

    Armon Sharei

    Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

  7. Rapid immune colloidal gold strip for cetacean meat restraining illegal trade and consumption: implications for conservation and public health.

    Science.gov (United States)

    Lo, Chieh; Chin, Li-Te; Chu, Chi-Shih; Wang, Yu-Ting; Chan, Kun-Wei; Yang, Wei-Cheng

    2013-01-01

    The consumption of cetacean meat is geographically common and often of undetermined sustainability. Besides, it can expose humans to contaminants and zoonotic pathogens. The illegality of possessing cetacean meat was likely under-reported in some countries due to lack of attention paid by the officials although DNA analysis of market products helped to show such practices. We developed two monoclonal antibodies against synthetic peptides of myoglobin (Mb) for constructing a rapid immune colloidal gold strip. Only cetacean Mb is capable of binding to both antibodies and presents positive signal while the Mb from other animals can bind only 1 of the antibodies and presents negative result. The strip for cetacean meat would be an applicable and cost-effective test for field inspectors and even the general public. It contributes to increase the reporting capacity and coverage of illegal cetacean meat possession, which has implications for global cetacean conservation and public health.

  8. TALENs-mediated gene disruption of myostatin produces a larger phenotype of medaka with an apparently compromised immune system.

    Science.gov (United States)

    Chiang, Yi-An; Kinoshita, Masato; Maekawa, Shun; Kulkarni, Amod; Lo, Chu-Fang; Yoshiura, Yasutoshi; Wang, Han-Ching; Aoki, Takashi

    2016-01-01

    Although myostatin, a suppressor of skeletal muscle development and growth, has been well studied in mammals, its function in fish remains unclear. In this study, we used a popular genome editing tool with high efficiency and target specificity (TALENs; transcription activator-like effector nucleases) to mutate the genome sequence of myostatin (MSTN) in medaka (Oryzias latipes). After the TALEN pair targeting OlMyostatin was injected into fertilized medaka eggs, mutant G0 fish carrying different TALENs-induced frameshifts in the OlMSTN coding sequence were mated together in order to transmit the mutant sequences to the F1 generation. Two F1 mutants with frameshifted myostatin alleles were then mated to produce the F2 generation, and these F2 OlMSTN null (MSTN(-/-)) medaka were evaluated for growth performance. The F2 fish showed significantly increased body length and weight compared to the wild type fish at the juvenile and post-juvenile stages. At the post-juvenile stage, the average body weight of the MSTN(-/-) medaka was ∼25% greater than the wild type. However, we also found that when the F3 generation were challenged with red spotted grouper nervous necrosis virus (RGNNV), the expression levels of the interferon-stimulated genes were lower than in the wild type, and the virus copy number was maintained at a high level. We therefore conclude that although the MSTN(-/-) medaka had a larger phenotype, their immune system appeared to be at least partially suppressed or undeveloped. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Regulation of immune responsiveness in vivo by disrupting an early T-cell signaling event using a cell-permeable peptide.

    Directory of Open Access Journals (Sweden)

    David M Guimond

    Full Text Available The inducible T cell kinase (ITK regulates type 2 (Th2 cytokines that provide defense against certain parasitic and bacterial infections and are involved in the pathogenesis of lung inflammation such as allergic asthma. Activation of ITK requires the interaction of its SH3 domain with the poly-proline region of its signaling partner, the SH2 domain containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76. The specific disruption of the ITK-SH3/SLP-76 poly-proline interaction in vitro by a cell-permeable competitive inhibitor peptide (R9-QQP interferes with the activation of ITK and the transduction of its cellular functions in T lymphocytes. In the present investigation, we assessed the effects of R9-QQP treatment on the induction of an in vivo immune response as represented by lung inflammation in a murine model of allergic asthma. We found that mice treated with R9-QQP and sensitized and challenged with the surrogate allergen ovalbumin (OVA display significant inhibition of lung inflammation in a peptide-specific manner. Thus, parameters of the allergic response, such as airway hyper-responsiveness, suppression of inflammatory cell infiltration, reduction of bronchial mucus accumulation, and production of relevant cytokines from draining lymph nodes were significantly suppressed. These findings represent the first demonstration of the biological significance of the interaction between ITK and SLP-76 in the induction of an immune response in a whole animal model and specifically underscore the significance of the ITK-SH3 domain interaction with the poly-proline region of SLP-76 in the development of an inflammatory response. Furthermore, the experimental approach of intracellular peptide-mediated inhibition might be applicable to the study of other important intracellular interactions thus providing a paradigm for dissecting signal transduction pathways.

  10. The Universality of the Rapid Neutron-capture Process Revealed by a Possible Disrupted Dwarf Galaxy Star

    Science.gov (United States)

    Casey, Andrew R.; Schlaufman, Kevin C.

    2017-12-01

    The rapid neutron-capture or r-process is thought to produce the majority of the heavy elements (Z> 30) in extremely metal-poor stars. The same process is also responsible for a significant fraction of the heavy elements in the Sun. This universality of the r-process is one of its characteristic features, as well as one of the most important clues to its astrophysical origin. We report the discovery of an extremely metal-poor field giant with [{Sr},{Ba}/{{H}}]≈ -6.0 and [{Sr},{Ba}/{Fe}]≈ -3.0, the lowest abundances of strontium and barium relative to iron ever observed. Despite its low abundances, the star 2MASS J151113.24-213003.0 has [{Sr}/{Ba}]=-0.11+/- 0.14, therefore its neutron-capture abundances are consistent with the main solar r-process pattern that has [{Sr}/{Ba}]=-0.25. It has been suggested that extremely low neutron-capture abundances are a characteristic of dwarf galaxies, and we find that this star is on a highly eccentric orbit with an apocenter ≳100 kpc that lies in the disk of satellites in the halo of the Milky Way. We show that other extremely metal-poor stars with low [Sr, Ba/H] and [Sr, Ba/Fe] plus solar [Sr/Ba] tend to have orbits with large apocenters, consistent with a dwarf galaxy origin for this class of object. The nucleosynthesis event that produced the neutron-capture elements in 2MASS J151113.24-213003.0 must produce both strontium and barium together in the solar ratio. We exclude contributions from the s-process in intermediate-mass asymptotic giant branch or fast-rotating massive metal-poor stars, pair-instability supernovae, the weak r-process, and neutron-star mergers. We argue that the event was a Pop III or extreme Pop II core-collapse supernova explosion. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

  11. Disruptions in JET

    International Nuclear Information System (INIS)

    Wesson, J.A.; Gill, R.D.; Hugon, M.

    1989-01-01

    In JET, both high density and low-q operation are limited by disruptions. The density limit disruptions are caused initially by impurity radiation. This causes a contraction of the plasma temperature profile and leads to an MHD unstable configuration. There is evidence of magnetic island formation resulting in minor disruptions. After several minor disruptions, a major disruption with a rapid energy quench occurs. This event takes place in two stages. In the first stage there is a loss of energy from the central region. In the second stage there is a more rapid drop to a very low temperature, apparently due to a dramatic increase in impurity radiation. The final current decay takes place in the resulting cold plasma. During the growth of the MHD instability the initially rotating mode is brought to rest. This mode locking is believed to be due to an electromagnetic interaction with the vacuum vessel and external magnetic field asymmetries. The low-q disruptions are remarkable for the precision with which they occur at q ψ = 2. These disruptions do not have extended precursors or minor disruptions. The instability grows and locks rapidly. The energy quench and current decay are generally similar to those of the density limit. (author). 43 refs, 35 figs, 3 tabs

  12. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Directory of Open Access Journals (Sweden)

    Genevieve E Martin

    Full Text Available Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+ T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001, soluble CD163 (sCD163, p = 0.001, sCD14 (p = 0.022, neopterin (p = 0.029 and an increased proportion of CD16(+ monocytes (p = 0.009 compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+ monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002 suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+ T lymphocytes.Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  13. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Science.gov (United States)

    Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M

    2013-01-01

    Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  14. 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

  15. 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...

  16. Social isolation disrupts innate immune responses in both male and female prairie voles and enhances agonistic behavior in female prairie voles (Microtus ochrogaster).

    Science.gov (United States)

    Scotti, Melissa-Ann L; Carlton, Elizabeth D; Demas, Gregory E; Grippo, Angela J

    2015-04-01

    Psychosocial stress, specifically social isolation, is an important risk factor for the development of a variety of psychological and physiological disorders. Changes in immune function have been hypothesized to mediate this relationship. The current study used the prairie vole (Microtus ochrogaster) model of isolation-induced depressive-like behavior to test whether social isolation led to changes in innate immune function. Specifically, we used hemolytic complement (CH50) and bacteria killing assays to assess innate immunity, in paired or singly housed male and female prairie voles. Further, in a second experiment we tested whether females exposed to an additional short-term social stressor, a resident-intruder trial, would show changes in immune function as well as enhanced hypothalamic pituitary axis (HPA) activity as indicated by elevated plasma corticosterone levels. Socially isolated animals, regardless of sex, had significantly reduced CH50s and bacteria killing ability. Socially isolated females exposed to a resident-intruder stressor also showed reduced CH50s and bacteria killing ability as well as significant increases in aggressive behavior, however, they did not show elevated circulating corticosterone levels. Collectively, these data will help inform our understanding of the relationship between social isolation and physiological and psychological health. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. 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

  18. Commercial herbal medicines used as African traditional medicines: Ngoma Herbal Tonic Immune Booster interferes with a rapid urine drug screening test.

    Science.gov (United States)

    Mothibe, M E; Osuch, E; Kahler-Venter, C P

    2017-08-25

    The prevalent use of African traditional medicine by the general public has been reported. With commercialisation and marketing, some of the herbal medicines (HMs) used are readily available over the counter, most of them promoted as immune boosters. These commercial HMs have not been taken through clinical trials and other tests that would validate their composition and safety, and other properties such as their effect on laboratory diagnostic tests. To investigate the cross-reactivity of selected HMs with commonly tested drugs of abuse (DoA) using a qualitative rapid urinalysis assay. The six HMs selected were bought from local pharmacies. A rapid urinalysis screening test was performed with the Instant View Multi-Drug of Abuse Test kit from Labstix Diagnostics. Drug-free urine (DFU) was pooled from samples donated by healthy volunteers. Urine samples that had tested positive for DoA were obtained from a pharmacology laboratory. Aliquots of the urine samples were spiked with the HMs in neat and diluted form, and tested at various time intervals. The results for the DFU samples spiked with the HMs remained negative. There were no significant changes in pH or specific gravity of the samples. The results of samples that had tested positive for tetrahydrocannabinol (THC) were not altered by five of the HMs when spiked at 40% v/v. The HM Ngoma Herbal Tonic Immune Booster caused false-negative results for the THC test. An important finding is that the herbal mixture Ngoma Herbal Tonic Immune Booster caused false-negative results for the cannabinoid screening test. It adds to the list of substances that may be potential adulterants of urine for screening tests.

  19. The use of the rapid osmotic fragility test as an additional test to diagnose canine immune-mediated haemolytic anaemia

    DEFF Research Database (Denmark)

    Paes, Geert; Paepe, Dominique; Meyer, Evelyne

    2013-01-01

    Background: Diagnosing canine immune-mediated haemolytic anaemia (IMHA) is often challenging because all currently available tests have their limitations. Dogs with IMHA often have an increased erythrocyte osmotic fragility (OF), a characteristic that is sometimes used in the diagnosis of IMHA...... hyperlipemic dogs (group 3), 10 dogs with lymphoma (group 4), 8 dogs with an infection (group 5) and 13 healthy dogs (group 6) were included. In all dogs, blood smear examination, in-saline auto-agglutination test, Coombs' test, COFT and ROFT were performed. In the COFT, OF5, OF50 and OF90 were defined...

  20. Early systemic bacterial dissemination and a rapid innate immune response characterize genetic resistance to plague of SEG mice.

    Science.gov (United States)

    Demeure, Christian E; Blanchet, Charlène; Fitting, Catherine; Fayolle, Corinne; Khun, Huot; Szatanik, Marek; Milon, Geneviève; Panthier, Jean-Jacques; Jaubert, Jean; Montagutelli, Xavier; Huerre, Michel; Cavaillon, Jean-Marc; Carniel, Elisabeth

    2012-01-01

    Although laboratory mice are usually highly susceptible to Yersinia pestis, we recently identified a mouse strain (SEG) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance. The kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in SEG and susceptible C57BL/6J mice after subcutaneous infection with the virulent Y. pestis CO92. Bacterial invasion occurred early (day 2) but was transient in SEG/Pas mice, whereas in C57BL/6J mice it was delayed but continuous until death. The bacterial load in all organs significantly correlated with the production of 5 cytokines (granulocyte colony-stimulating factor, keratinocyte-derived chemokine (KC), macrophage cationic peptide-1 (MCP-1), interleukin 1α, and interleukin 6) involved in monocyte and neutrophil recruitment. Indeed, higher proportions of these 2 cell types in blood and massive recruitment of F4/80(+)CD11b(-) macrophages in the spleen were observed in SEG/Pas mice at an early time point (day 2). Later times after infection (day 4) were characterized in C57BL/6J mice by destructive lesions of the spleen and impaired granulopoiesis. A fast and efficient Y. pestis dissemination in SEG mice may be critical for the triggering of an early and effective innate immune response necessary for surviving plague.

  1. The apolipoprotein L family of programmed cell death and immunity genes rapidly evolved in primates at discrete sites of host-pathogen interactions.

    Science.gov (United States)

    Smith, Eric E; Malik, Harmit S

    2009-05-01

    Apolipoprotein L1 (APOL1) is a human protein that confers immunity to Trypanosoma brucei infections but can be countered by a trypanosome-encoded antagonist SRA. APOL1 belongs to a family of programmed cell death genes whose proteins can initiate host apoptosis or autophagic death. We report here that all six members of the APOL gene family (APOL1-6) present in humans have rapidly evolved in simian primates. APOL6, furthermore, shows evidence of an adaptive sweep during recent human evolution. In each APOL gene tested, we found rapidly evolving codons in or adjacent to the SRA-interacting protein domain (SID), which is the domain of APOL1 that interacts with SRA. In APOL6, we also found a rapidly changing 13-amino-acid cluster in the membrane-addressing domain (MAD), which putatively functions as a pH sensor and regulator of cell death. We predict that APOL genes are antagonized by pathogens by at least two distinct mechanisms: SID antagonists, which include SRA, that interact with the SID of various APOL proteins, and MAD antagonists that interact with the MAD hinge base of APOL6. These antagonists either block or prematurely cause APOL-mediated programmed cell death of host cells to benefit the infecting pathogen. These putative interactions must occur inside host cells, in contrast to secreted APOL1 that trafficks to the trypanosome lysosome. Hence, the dynamic APOL gene family appears to be an important link between programmed cell death of host cells and immunity to pathogens.

  2. Disrupted Disclosure

    DEFF Research Database (Denmark)

    Krause Hansen, Hans; Uldam, Julie

    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...

  3. Family Disruptions

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Disruptions Page Content Article Body No matter how ...

  4. Digital Disruption

    DEFF Research Database (Denmark)

    Rosenstand, Claus Andreas Foss

    det digitale domæne ud over det niveau, der kendetegner den nuværende debat, så præsenteres der ny viden om digital disruption. Som noget nyt udlægges Clayton Christens teori om disruptiv innovation med et særligt fokus på små organisationers mulighed for eksponentiel vækst. Specielt udfoldes...... forholdet mellem disruption og den stadig accelererende digitale udvikling i konturerne til ny teoridannelse om digital disruption. Bogens undertitel ”faretruende og fascinerende forandringer” peger på, at der er behov for en nuanceret debat om digital disruption i modsætning til den tone, der er slået an i...... 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...

  5. Polybrominated Diphenyl Ethers Orally Administration to Mice Were Tansferred to Offspring during Gestation and Lactation with Disruptions on the Immune System.

    Science.gov (United States)

    Hong, Soon Keun; Sohn, Kyung Hee; Kim, In Young; Lee, Jong Kwon; Ju, Jung Hun; Kim, Jin Ho; Lim, Chae Hyung; Han, Beom Seok; Jung, Hwa Chul; Lee, Jin Yong; Park, Kui Lea

    2010-04-01

    The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings. In this study, mated female C57BL/6J mice were orally administered penta-BDE, deca-BDE or corn oil for 5 weeks, from gestational day 6 to lactational day 21. The body weight of PND21 exposed to penta-BDE was significantly decreased relative to control mice, but that of post-natal day 63 (PND63) were recovered. Orally dosed dams with penta-BDE had significantly smaller absolute and relative spleen masses than control mice. Absolute and relative spleen and thymus masses of PND21 exposed to penta-BDE were significantly decreased over control. The exposure of dams and PND21 with penta-BDE reduced the number of splenocytes and thymocytes. As results of hematologic analysis, percentage WBC and percentage neutrophils increased in dams with deca-BDE. Splenic T cell proliferation in dams and PND21 exposed to penta-BDE was increased, and there were no significant difference in splenic B cell proliferation in all treatment groups. As results of flow cytometric analysis of splenocyte, percentage total T cell, Th cell and Tc cell in PND21 exposed to penta-BDE was slightly increased, and percentage macrophage in dams and PND21 exposed to deca-BDE was decreased. The ELISA results of antibody production show no significant difference in all treatment groups relative to controls. These results imply that PBDEs given to the dam were transferred to the offspring during gestation and lactation, and PBDEs transferred from the dam affect immune system of offspring.

  6. A lack of immune system genes causes loss in high frequency hearing but does not disrupt cochlear synapse maturation in mice.

    Science.gov (United States)

    Calton, Melissa A; Lee, Dasom; Sundaresan, Srividya; Mendus, Diana; Leu, Rose; Wangsawihardja, Felix; Johnson, Kenneth R; Mustapha, Mirna

    2014-01-01

    Early cochlear development is marked by an exuberant outgrowth of neurites that innervate multiple targets. The establishment of mature cochlear neural circuits is, however, dependent on the pruning of inappropriate axons and synaptic connections. Such refinement also occurs in the central nervous system (CNS), and recently, genes ordinarily associated with immune and inflammatory processes have been shown to play roles in synaptic pruning in the brain. These molecules include the major histocompatibility complex class I (MHCI) genes, H2-K(b) and H2-D(b), and the complement cascade gene, C1qa. Since the mechanisms involved in synaptic refinement in the cochlea are not well understood, we investigated whether these immune system genes may be involved in this process and whether they are required for normal hearing function. Here we report that these genes are not necessary for normal synapse formation and refinement in the mouse cochlea. We further demonstrate that C1qa expression is not necessary for normal hearing in mice but the lack of expression of H2-K(b) and H2-D(b) causes hearing impairment. These data underscore the importance of the highly polymorphic family of MHCI genes in hearing in mice and also suggest that factors and mechanisms regulating synaptic refinement in the cochlea may be distinct from those in the CNS.

  7. Disruptions of Host Immunity and Inflammation by Giardia Duodenalis: Potential Consequences for Co-Infections in the Gastro-Intestinal Tract

    Directory of Open Access Journals (Sweden)

    James A. Cotton

    2015-11-01

    Full Text Available Giardia duodenalis (syn. G. intestinalis, or G. lamblia is a leading cause of waterborne diarrheal disease that infects hundreds of millions of people annually. Research on Giardia has greatly expanded within the last few years, and our understanding of the pathophysiology and immunology on this parasite is ever increasing. At peak infection, Giardia trophozoites induce pathophysiological responses that culminate in the development of diarrheal disease. However, human data has suggested that the intestinal mucosa of Giardia-infected individuals is devoid of signs of overt intestinal inflammation, an observation that is reproduced in animal models. Thus, our understanding of host inflammatory responses to the parasite remain incompletely understood and human studies and experimental data have produced conflicting results. It is now also apparent that certain Giardia infections contain mechanisms capable of modulating their host’s immune responses. As the oral route of Giardia infection is shared with many other gastrointestinal (GI pathogens, co-infections may often occur, especially in places with poor sanitation and/or improper treatment of drinking water. Moreover, Giardia infections may modulate host immune responses and have been found to protect against the development of diarrheal disease in developing countries. The following review summarizes our current understanding of the immunomodulatory mechanisms of Giardia infections and their consequences for the host, and highlights areas for future research. Potential implications of these immunomodulatory effects during GI co-infection are also discussed.

  8. 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....

  9. 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...

  10. Immunization by intrabronchial administration to 1-week-old foals of an unmarked double gene disruption strain of Rhodococcus equi strain 103+.

    Science.gov (United States)

    Pei, Yanlong; Nicholson, Vivian; Woods, Katharine; Prescott, John F

    2007-11-15

    Rhodococcus equi causes fatal granulomatous pneumonia in foals and immunocompromised animals and humans. However, there is no effective vaccine against this infection. In this study, the chromosomal genes isocitrate lyase (icl) and cholesterol oxidase (choE) were chosen as targets for mutation and assessment of the double mutant as an intrabronchial vaccine in 1-week-old foals. Using a modification of a suicide plasmid previously developed in this laboratory, we developed a choE-icl unmarked deletion mutant of R. equi strain 103+. Five 1-week-old foals were infected intrabronchially with the mutant and challenged intrabronchially with the parent, virulent, strain 2 weeks later. Three of the foals were protected against pneumonia caused by the virulent strain, but the other two foals developed pneumonia caused by the mutant strain during the post-challenge period. Since infection of 3-week-old foals by an icl mutant in an earlier study had shown complete attenuation of the strain, we conclude that a proportion of foals in the 1st week or so of life are predisposed to developing R. equi pneumonia because of an inability to mount an effective immune response. This has been suspected previously but this is the first time that this has been demonstrated experimentally.

  11. Systematic literature review comparing rapid 3-dose administration of the GSK tick-borne encephalitis vaccine with other primary immunization schedules.

    Science.gov (United States)

    Galgani, Ilaria; Bunge, Eveline M; Hendriks, Lisa; Schludermann, Christopher; Marano, Cinzia; De Moerlooze, Laurence

    2017-09-01

    Tick-borne encephalitis (TBE), which is endemic across large regions of Europe and Asia, is most effectively prevented through vaccination. Three-dose primary TBE vaccination schedules are either rapid (0,7,21-days) or conventional (0,28-84-days, 9-12-months). The second dose can also be administered at 14 days for faster priming and sero-protection). Areas covered: We used a three-step selection process to identify 21 publications comparing the immunogenicity and/or safety of different schedules. Expert commentary: Priming with two or three TBE vaccine doses was highly immunogenic. After conventional priming (0-28 days), 95% adults and ≥95% children had neutralization test (NT) titers ≥10 at 14 days post-dose-2 compared with 92% adults and 99% children at 21 days post-dose-3 (rapid schedule). Most subjects retained NT titers ≥10 at day 300. A single booster dose induced a strong immune response in all subjects irrespective of primary vaccination schedule or elapsed time since priming. GMT peaked at 42 days post-dose-1 (i.e., 21 days post-dose 3 [rapid-schedule], or 14-28 days post-dose-2 [conventional-schedule]), and declined thereafter. Adverse events were generally rare and declined with increasing doses. In the absence of data to recommend one particular schedule, the regimen choice will remain at the physician's discretion, based on patient constraints and availability.

  12. A high force of plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in papua new guinean children.

    Directory of Open Access Journals (Sweden)

    Cristian Koepfli

    Full Text Available When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax ((molFOB, i.e. the number of genetically distinct blood-stage infections over time, and compared it to previously reported values for P. falciparum.P. vivax (molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1-4.5 years.On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with mol FOB (incidence rate ratio (IRR = 1.99, 95% confidence interval (CI95 [1.80, 2.19], (molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001 compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02.P. vivax (molFOB is considerably higher than P. falciparum (molFOB (5.5 clones/child/year-at-risk. The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.

  13. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Solt, Anna C; Henríquez-Roldán, Carlos; Torres-Jardón, Ricardo; Nuse, Bryan; Herritt, Lou; Villarreal-Calderón, Rafael; Osnaya, Norma; Stone, Ida; García, Raquel; Brooks, Diane M; González-Maciel, Angelica; Reynoso-Robles, Rafael; Delgado-Chávez, Ricardo; Reed, William

    2008-02-01

    Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

  14. Targeted disruption in mice of a neural stem cell-maintaining, KRAB-Zn finger-encoding gene that has rapidly evolved in the human lineage.

    Directory of Open Access Journals (Sweden)

    Huan-Chieh Chien

    Full Text Available Understanding the genetic basis of the physical and behavioral traits that separate humans from other primates is a challenging but intriguing topic. The adaptive functions of the expansion and/or reduction in human brain size have long been explored. From a brain transcriptome project we have identified a KRAB-Zn finger protein-encoding gene (M003-A06 that has rapidly evolved since the human-chimpanzee separation. Quantitative RT-PCR analysis of different human tissues indicates that M003-A06 expression is enriched in the human fetal brain in addition to the fetal heart. Furthermore, analysis with use of immunofluorescence staining, neurosphere culturing and Western blotting indicates that the mouse ortholog of M003-A06, Zfp568, is expressed mainly in the embryonic stem (ES cells and fetal as well as adult neural stem cells (NSCs. Conditional gene knockout experiments in mice demonstrates that Zfp568 is both an NSC maintaining- and a brain size-regulating gene. Significantly, molecular genetic analyses show that human M003-A06 consists of 2 equilibrated allelic types, H and C, one of which (H is human-specific. Combined contemporary genotyping and database mining have revealed interesting genetic associations between the different genotypes of M003-A06 and the human head sizes. We propose that M003-A06 is likely one of the genes contributing to the uniqueness of the human brain in comparison to other higher primates.

  15. The rapid-onset dystonia parkinsonism mutation D923N of the Na+, K+-ATPase alpha3 isoform disrupts Na+ interaction at the third Na+ site.

    Science.gov (United States)

    Einholm, Anja Pernille; Toustrup-Jensen, Mads S; Holm, Rikke; Andersen, Jens Peter; Vilsen, Bente

    2010-08-20

    Rapid-onset dystonia parkinsonism (RDP), a rare neurological disorder, is caused by mutation of the neuron-specific alpha3-isoform of Na(+), K(+)-ATPase. Here, we present the functional consequences of RDP mutation D923N. Relative to the wild type, the mutant exhibits a remarkable approximately 200-fold reduction of Na(+) affinity for activation of phosphorylation from ATP, reflecting a defective interaction of the E(1) form with intracellular Na(+). This is the largest effect on Na(+) affinity reported so far for any Na(+), K(+)-ATPase mutant. D923N also affects the interaction with extracellular Na(+) normally driving the E(1)P to E(2)P conformational transition backward. However, no impairment of K(+) binding was observed for D923N, leading to the conclusion that Asp(923) is specifically associated with the third Na(+) site that is selective toward Na(+). The crystal structure of the Na(+), K(+)-ATPase in E(2) form shows that Asp(923) is located in the cytoplasmic half of transmembrane helix M8 inside a putative transport channel, which is lined by residues from the transmembrane helices M5, M7, M8, and M10 and capped by the C terminus, recently found involved in recognition of the third Na(+) ion. Structural modeling of the E(1) form of Na(+), K(+)-ATPase based on the Ca(2+)-ATPase crystal structure is consistent with the hypothesis that Asp(923) contributes to a site binding the third Na(+) ion. These results in conjunction with our previous findings with other RDP mutants suggest that a selective defect in the handling of Na(+) may be a general feature of the RDP disorder.

  16. A simple and rapid Hepatitis A Virus (HAV titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

    Directory of Open Access Journals (Sweden)

    Kaplan Gerardo G

    2008-12-01

    Full Text Available Abstract Background Hepatitis A virus (HAV, the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the

  17. 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

  18. 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....... 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...... 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...

  19. 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. ...

  20. 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.

  1. Investing in Immunity: Prepandemic Immunization to Combat Future Influenza Pandemics.

    Science.gov (United States)

    Goodman, Jesse L

    2016-02-15

    We are unlikely, with current technologies, to have sufficient pandemic influenza vaccine ready in time to impact the first wave of the next pandemic. Emerging data show that prior immunization with an immunologically distinct hemagglutinin of the same subtype offers the potential to "prime" recipients for rapid protection with a booster dose, years later, of a vaccine then manufactured to match the pandemic strain. This article proposes making prepandemic priming vaccine(s) available for voluntary use, particularly to those at high risk of early occupational exposure, such as first responders and healthcare workers, and to others maintaining critical infrastructure. In addition to providing faster protection and potentially reducing social disruption, being able, early in a pandemic, to immunize those who had received prepandemic vaccine with one dose of the pandemic vaccine, rather than the 2 doses typically required, would reduce the total doses of pandemic vaccine then needed, extending vaccine supplies. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Prenatal Alcohol Exposure and the Developing Immune System

    OpenAIRE

    Gauthier, Theresa W.

    2015-01-01

    Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensiv...

  3. Clustered lot quality assurance sampling: a tool to monitor immunization coverage rapidly during a national yellow fever and polio vaccination campaign in Cameroon, May 2009.

    Science.gov (United States)

    Pezzoli, L; Tchio, R; Dzossa, A D; Ndjomo, S; Takeu, A; Anya, B; Ticha, J; Ronveaux, O; Lewis, R F

    2012-01-01

    We used the clustered lot quality assurance sampling (clustered-LQAS) technique to identify districts with low immunization coverage and guide mop-up actions during the last 4 days of a combined oral polio vaccine (OPV) and yellow fever (YF) vaccination campaign conducted in Cameroon in May 2009. We monitored 17 pre-selected districts at risk for low coverage. We designed LQAS plans to reject districts with YF vaccination coverage LQAS proved to be useful in guiding the campaign vaccination strategy before the completion of the operations.

  4. Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection.

    Science.gov (United States)

    Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R

    2012-04-30

    Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Origins of adaptive immunity.

    Science.gov (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  6. 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)

  7. Lethal inflammasome activation by a multi-drug resistant pathobiont upon antibiotic disruption of the microbiota

    Science.gov (United States)

    Ayres, Janelle S.; Trinidad, Norver J.; Vance, Russell E.

    2012-01-01

    The mammalian intestine harbors a complex microbial community that provides numerous benefits to its host. However, the microbiota can also include potentially virulent species, termed pathobionts, which can cause disease when intestinal homeostasis is disrupted. The molecular mechanisms by which pathobionts cause disease remain poorly understood. Here we describe a sepsis-like disease that occurs upon gut injury in antibiotic-treated mice. Sepsis was associated with the systemic spread of a specific multidrug-resistant E. coli pathobiont that expanded dramatically in the microbiota of antibiotic-treated mice. Rapid sepsis-like death required a component of the innate immune system, the Naip5-Nlrc4 inflammasome. In accordance with Koch's postulates, we found the E. coli pathobiont was sufficient to activate Naip5-Nlrc4 and cause disease when injected intravenously into unmanipulated mice. These findings reveal how sepsis-like disease can result from recognition of pathobionts by the innate immune system. PMID:22522562

  8. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  9. [Current development of rapid high-throughout determination technology for total components of traditional Chinese medicines and formula and synthetic immunity chip method].

    Science.gov (United States)

    He, Fu-Yuan; Deng, Kai-Wen; Zeng, Jiao-Li; Dai, Ru-Wen; Dai, Ru-Wen; Xia, Zan-Shao; Liu, Weng-Long; Shi, Ji-Lian

    2012-10-01

    The qualitative and quantitative analysis on traditional Chinese medicine and formula components can be made by chemical and instrumental analysis methods. Of both, the instrumental analysis methods play a dominant role, including HPLC, HPLC-MS, HPLC-NMR, GC, GC-MS, biochemical and biological effect. But because traditional Chinese medicines and formula have complicated components, chemical methods are so unspecific that they shall be used less or with caution. While instrumental analysis methods are so specific that they are appropriate for analyzing complicated single component. The analysis techniques for multiple components of traditional Chinese medicines and formula focus on fingerprints, but all of these analysis techniques are limited by the pre-requisite of separation and the lack of general-purpose detectors and therefore being hard to realize the determination of all components of traditional Chinese medicines and formula. In the natural world, however, organisms identify native and alien components through specificity and non-specificity of clusters decided by antigens and antibodies. For example, components of traditional Chinese medicines are directly or indirectly synthesized into antigens and injected into animals, in order to generate specific antibodies and then collect cross reaction information of these components to specific antibodies. As for components without cross reaction, their contents shall be directly read out on the basis of the inhibition rate curve of competitive reaction for specificity of antigens and antibodies. Besides, a cross inhibition rate matrix shall be established first, and them a multiple regression linear equation between cross component concentration or concentration logarithm and inhibition rate by labeling the immunity competitive reaction between antibodies and haptens of traditional Chinese medicine and compound components, and then solved to obtain concentration of each component. The two results are combined to

  10. Apps for immunization: Leveraging mobile devices to place the individual at the center of care.

    Science.gov (United States)

    Wilson, Kumanan; Atkinson, Katherine M; Westeinde, Jacqueline

    2015-01-01

    Mobile technology and applications (apps) have disrupted several industries including healthcare. The advantage of apps, being personally focused and permitting bidirectional communication, make them well suited to address many immunization challenges. As of April 25, 2015 searching the Android app store with the words 'immunize app' and 'immunization app' in Canada yielded 225 apps. On the Apple App Store a similar search produced 98 results. These include apps that provide immunization related information, permit vaccine tracking both for individuals and for animals, assist with the creation of customized schedules and identification of vaccine clinics and serve as sources of education. The diverse functionality of mobile apps creates the potential for transformation of immunization practice both at a personal level and a system level. For individuals, mobile apps offer the opportunity for better record keeping, assistance with the logistics of vaccination, and novel ways of communicating with and receiving information from public health officials. For the system, mobile apps offer the potential to improve the quality of information residing in immunization information systems and program evaluation, facilitate harmonization of immunization information between individuals, health care providers and public health as well as reduce vaccine hesitancy. As mobile technology continues to rapidly evolve there will emerge new ways in which apps can enhance immunization practice.

  11. Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1, H3N2 and H1N1 viruses.

    Directory of Open Access Journals (Sweden)

    Graeme E Price

    2010-10-01

    Full Text Available The sudden emergence of novel influenza viruses is a global public health concern. Conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. In contrast, "universal" vaccines targeting conserved viral components could be used regardless of viral strain or subtype. Previous approaches to universal vaccination have required protracted multi-dose immunizations. Here we evaluate a single dose universal vaccine strategy using recombinant adenoviruses (rAd expressing the conserved influenza virus antigens matrix 2 and nucleoprotein.In BALB/c mice, administration of rAd via the intranasal route was superior to intramuscular immunization for induction of mucosal responses and for protection against highly virulent H1N1, H3N2, or H5N1 influenza virus challenge. Mucosally vaccinated mice not only survived, but had little morbidity and reduced lung virus titers. Protection was observed as early as 2 weeks post-immunization, and lasted at least 10 months, as did antibodies and lung T cells with activated phenotypes. Virus-specific IgA correlated with but was not essential for protection, as demonstrated in studies with IgA-deficient animals.Mucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic.

  12. Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-alpha Release by Mononuclear Cells in Healthy Adults

    NARCIS (Netherlands)

    Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost

    2016-01-01

    OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,

  13. Internal disruption in tokamaks

    International Nuclear Information System (INIS)

    Kuvshinov, B.N.; Savrukhin, P.V.

    1990-01-01

    A review of results of experimental and theoretical investigations of internal disruption in tokamaks is given. Specific features of various types of saw-tooth oscillations are described and their classification is performed. Theoretical models of the process of development of internal disruption instability are discussed. Effect of internal disruption on parameters of plasma, confined in tokamak, is considered. Scalings of period and amplitude of saw-tooth oscillations, as well as version radius are presented. Different methods for stabilizing instability of internal disruption are described

  14. Internal disruptions in tokamaks

    International Nuclear Information System (INIS)

    Kuvshinov, B.N.; Savrukhin, P.V.

    1990-01-01

    Experimental and theoretical studies of the phenomenon of internal disruptions in tokamaks are reviewed. A classification scheme is introduced and the features of different types of sawtooth oscillations are described. A theoretical model for the development of the internal disruption instability is discussed. The effect of internal disruptions on the parameters of plasma confined in tokamaks is discussed. Scaling laws for the period and amplitude of sawtooth oscillations, as well as for the inversion radius, are presented. Different methods of stabilizing the internal disruption instability are described

  15. Pentraxins and immunity

    Directory of Open Access Journals (Sweden)

    Priya Nagar

    2014-01-01

    Full Text Available Pentraxin-3 (PTX3 is a multifactorial protein involved in immunity and inflammation, which is rapidly produced and released by several cell types in response to inflammatory signals. It may be suggested that PTX3 is related to periodontal tissue inflammation. Its salivary concentrations may have a diagnostic potential. Pentraxin-3 (PTX3 is an ancient family of multifactorial proteins involved in immunity and inflammation. They are rapidly produced and released by various types of cells when there are indications of inflammation. PTX3 is related to inflammation in the periodontal tissue and it can be suggested that salivary concentrations may be used for diagnosing the same.

  16. Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice

    International Nuclear Information System (INIS)

    Jenkins, Darlene E; Hornig, Yvette S; Oei, Yoko; Dusich, Joan; Purchio, Tony

    2005-01-01

    Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4–6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at

  17. Disruptions in Tokamaks

    International Nuclear Information System (INIS)

    Bondeson, A.

    1987-01-01

    This paper discusses major and minor disruptions in Tokamaks. A number of models and numerical simulations of disruptions based on resistive MHD are reviewed. A discussion is given of how disruptive current profiles are correlated with the experimentally known operational limits in density and current. It is argued that the q a =2 limit is connected with stabilization of the m=2/n=1 tearing mode for a approx.< 2.7 by resistive walls and mode rotation. Experimental and theoretical observations indicate that major disruptions usually occur in at least two phases, first a 'predisruption', or loss of confinement in the region 1 < q < 2, leaving the q approx.= 1 region almost unaffected, followed by a final disruption of the central part, interpreted here as a toroidal n = 1 external kink mode. (author)

  18. A novel rapid direct haemagglutination-inhibition assay for measurements of humoral immune response against non-haemagglutinating Fowlpox virus strains in vaccinated chickens.

    Science.gov (United States)

    Wambura, Philemon N; Mzula, Alexanda

    2017-10-01

    Fowlpox (FP) is a serious disease in chickens caused by Fowlpox virus (FPV). One method currently used to control FPV is vaccination followed by confirmation that antibody titres are protective using the indirect haemagglutination assay (IHA). The direct haemagglutination inhibition (HI) assay is not done because most FPV strains do not agglutinate chicken red blood cells (RBCs). A novel FPV strain TPV-1 which agglutinates chicken RBCs was discovered recently and enabled a direct HI assay to be conducted using homologous sera. This study is therefore aimed at assessing the direct HI assay using a recently discovered novel haemagglutinating FPV strain TPV-1 in chickens vaccinated with a commercial vaccine containing a non-haemagglutinating FPV.Chicks vaccinated with FPV at 1 day-old had antibody geometric mean titres (GMT) of log 2 3.7 at 7 days after vaccination and log 2 8.0 at 28 days after vaccination when tested in the direct HI. Chickens vaccinated at 6 weeks-old had antibody geometric mean titres (GMT) of log 2 5.0 at 7 days after vaccination and log 2 8.4 at 28 days after vaccination when tested in the direct HI. The GMT recorded 28 days after vaccination was slightly higher in chickens vaccinated at 6-week-old than in chicks vaccinated at one-day-old. However, this difference was not significant (P > 0.05). All vaccinated chickens showed "takes". No antibody response to FPV and "takes" were detected in unvaccinated chickens (GMT 0.05). These findings indicate that a simple and rapid direct HI assay using the FPV TPV-1 strain as antigen may be used to measure antibody levels in chickens vaccinated with non-haemagglutinating strains of FPV, and that the titres are comparable to those obtained by indirect IHA.

  19. Rapid surveillance for health events following a mass meningococcal B vaccine program in a university setting: A Canadian Immunization Research Network study.

    Science.gov (United States)

    Langley, J M; MacDougall, D M; Halperin, B A; Swain, A; Halperin, S A; Top, K A; McNeil, S A; MacKinnon-Cameron, D; Marty, K; De Serres, G; Dubé, E; Bettinger, J A

    2016-07-25

    An outbreak of Neisseria meningitidis serotype B infection occurred at a small residential university; public health announced an organizational vaccination program with the 4-component Meningococcal B (4CMenB) vaccine (Bexsero(TM), Novartis/GlaxoSmithKline Inc.) several days later. Since there were limited published data on reactogenicity of 4CMenB in persons over 17years of age, this study sought to conduct rapid surveillance of health events in vaccinees and controls using an online survey. Vaccine uptake was 84.7% for dose 1 (2967/3500) and 70% (2456/3500) for dose 2; the survey response rates were 33.0% (987/2967) and 18.7% (459/2456) in dose 1 and dose 1 recipients respectively, and 12% in unvaccinated individuals (63/533). Most students were 20-29years of age (vaccinees, 64.0%; controls, 74.0). A new health problem or worsening of an existing health problem was reported by 30.0% and 30.3% of vaccine recipients after doses 1 and 2 respectively; and by 15.9% of controls. These health problems interfered with the ability to perform normal activities in most vaccinees reporting these events (74.7% post dose 1; 62.6% post dose 2), and in 60% of controls. The health problems led to a health care provider visit (including emergency room) in 12.8% and 14.4% of vaccinees post doses 1 and 2, respectively and in 40% of controls. The most common reactions in vaccinees were injection site reactions (20.6% post dose 1, 16.1% post dose 20 and non-specific systemic complaints (22.6% post dose 1, 17.6% post dose 2). No hospitalizations were reported. An online surveillance program during an emergency meningococcal B vaccine program was successfully implemented, and detected higher rates of health events in vaccinees compared to controls, and high rates of both vaccinees and controls seeking medical attention. The types of adverse events reported by young adult vaccinees were consistent with those previously. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Endocrine Disrupting Contaminants—Beyond the Dogma

    Science.gov (United States)

    Guillette, Louis J.

    2006-01-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

  1. Pauci-immune necrotizing glomerulonephritis

    NARCIS (Netherlands)

    Rutgers, Abraham; Sanders, Jan S F; Stegeman, Coen A; Kallenberg, Cees G M

    Pauci-immune necrotizing glomerulonephritis is the most frequent cause of rapidly progressive glomerulonephritis and, in most cases, is associated with antineutrophil cytoplasmic antibodies (ANCA). It is either the renal manifestation of Wegener's granulomatosis, microscopic polyangiitis of

  2. Prenatal Alcohol Exposure and the Developing Immune System.

    Science.gov (United States)

    Gauthier, Theresa W

    2015-01-01

    Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

  3. Understanding disruptions in tokamaksa)

    Science.gov (United States)

    Zakharov, Leonid E.; Galkin, Sergei A.; Gerasimov, Sergei N.; contributors, JET-EFDA

    2012-05-01

    This paper describes progress achieved since 2007 in understanding disruptions in tokamaks, when the effect of plasma current sharing with the wall was introduced into theory. As a result, the toroidal asymmetry of the plasma current measurements during vertical disruption event (VDE) on the Joint European Torus was explained. A new kind of plasma equilibria and mode coupling was introduced into theory, which can explain the duration of the external kink 1/1 mode during VDE. The paper presents first results of numerical simulations using a free boundary plasma model, relevant to disruptions.

  4. Childhood Immunization

    Science.gov (United States)

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  5. Immunizations - diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  6. Disruption Physics and Mitigation on DIII-D

    International Nuclear Information System (INIS)

    Whyte, D.G.; Humphreys, D.A.; Kellman, A.G.

    2005-01-01

    The contributions of the DIII-D tokamak toward the understanding and control of disruptions are reviewed. Disruptions are found to be deterministic, and the underlying causes of disruption can therefore be predicted and avoided. With sufficiently rapid detection, possible damage from disruptions can be mitigated using an understanding of disruption phenomenology and plasma physics. Regimes of high β are readily available in DIII-D and provide access to relatively high energy density disruptions, despite DIII-D's moderate magnetic field and size. DIII-D, with all-graphite wall armor and wall conditioning between discharges, has proven highly resilient to the deleterious effects that disruptions can have on plasma operations. Simultaneously, exploitation and adaptation of DIII-D's extensive core and edge plasma diagnostic set have allowed for unique plasma measurements during disruptions. These measurements have tied into the development of several physical models used to understand aspects of disruptions, such as magnetohydrodynamic growth at the disruption onset, radiation energy balance through the thermal quench, and halo currents during the current quench. Based on this fundamental understanding, DIII-D has developed techniques to mitigate the harmful effects of disruptions by radiative dissipation of the plasma energy and extrapolated these techniques for possible use on larger devices like ITER

  7. Disruptive Mood Dysregulation Disorder

    Science.gov (United States)

    ... Application Process Managing Grants Clinical Research Training Small Business Research Labs at NIMH Labs at NIMH Home Research ... Chat on Disruptive Mood Dysregulation Disorder (Archived Transcript) Research and ... Journal Articles: References and abstracts from MEDLINE/PubMed (National ...

  8. 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.

  9. Development of disruption thermal analysis code DREAM

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Seiichiro; Kobayahsi, Takeshi [Kawasaki Heavy Industries Ltd., Kobe (Japan); Seki, Masahiro

    1989-07-01

    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).

  10. 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)

  11. Immunization Coverage

    Science.gov (United States)

    ... room/fact-sheets/detail/immunization-coverage","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... Plan Global Health Observatory (GHO) data - Immunization More information on vaccines and immunization News 1 in 10 ...

  12. Search and Disrupt

    DEFF Research Database (Denmark)

    Ørding Olsen, Anders

    . 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...... to influence from individual strategic interests on the outcomes. More generally, this points to the need for understanding the two-way influence of sources, rather than viewing external search as one-way knowledge accessing....

  13. Comparison of the efficiency of antibody selection from semi-synthetic scFv and non-immune Fab phage display libraries against protein targets for rapid development of diagnostic immunoassays.

    Science.gov (United States)

    Chan, Conrad E Z; Chan, Annie H Y; Lim, Angeline P C; Hanson, Brendon J

    2011-10-28

    Rapid development of diagnostic immunoassays against novel emerging or genetically modified pathogens in an emergency situation is dependent on the timely isolation of specific antibodies. Non-immune antibody phage display libraries are an efficient in vitro method for selecting monoclonal antibodies and hence ideal in these circumstances. Such libraries can be constructed from a variety of sources e.g. B cell cDNA or synthetically generated, and use a variety of antibody formats, typically scFv or Fab. However, antibody source and format can impact on the quality of antibodies generated and hence the effectiveness of this methodology for the timely production of antibodies. We have carried out a comparative screening of two antibody libraries, a semi-synthetic scFv library and a human-derived Fab library against the protective antigen toxin component of Bacillus anthracis and the epsilon toxin of Clostridium botulinum. We have shown that while the synthetic library produced a diverse collection of specific scFv-phage, these contained a high frequency of unnatural amber stops and glycosylation sites which limited their conversion to IgG, and also a high number which lost specificity when expressed as IgG. In contrast, these limitations were overcome by the use of a natural human library. Antibodies from both libraries could be used to develop sandwich ELISA assays with similar sensitivity. However, the ease and speed with which full-length IgG could be generated from the human-derived Fab library makes screening this type of library the preferable method for rapid antibody generation for diagnostic assay development. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Immunizing Children

    Directory of Open Access Journals (Sweden)

    Geraldine Jody Macdonald

    2014-11-01

    Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

  15. 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

  16. Quantitative Methods for Measuring Repair Rates and Innate-Immune Cell Responses in Wounded Mouse Skin.

    Science.gov (United States)

    Li, Zhi; Gothard, Elizabeth; Coles, Mark C; Ambler, Carrie A

    2018-01-01

    In skin wounds, innate-immune cells clear up tissue debris and microbial contamination, and also secrete cytokines and other growth factors that impact repair process such as re-epithelialization and wound closure. After injury, there is a rapid influx and efflux of immune cells at wound sites, yet the function of each innate cell population in skin repair is still under investigation. Flow cytometry is a valuable research tool for detecting and quantifying immune cells; however, in mouse back skin, the difficulty in extracting immune cells from small area of skin due to tissue complexity has made cytometric analysis an underutilized tool. In this paper, we provide detailed methods on the digestion of lesion-specific skin without disrupting antigen expression followed by multiplex cell staining that allows for identification of seven innate-immune populations, including rare subsets such as group-3 innate lymphoid cells (ILC3s), by flow-cytometry analysis. Furthermore, when studying the functions of immune cells to tissue repair an important metric to monitor is size of the wound opening. Normal wounds close steadily albeit at non-linear rates, while slow or stalled wound closure can indicate an underlying problem with the repair process. Calliper measurements are difficult and time-consuming to obtain and can require repeated sedation of experimental animals. We provide advanced methods for measuring of wound openness; digital 3D image capture and semi-automated image processing that allows for unbiased, reliable measurements that can be taken repeatedly over time.

  17. 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.

  18. 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

  19. Immunity's fourth dimension: approaching the circadian-immune connection.

    Science.gov (United States)

    Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

    2012-12-01

    The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Overvoltage protection for magnetic system during disruption in tokamak

    International Nuclear Information System (INIS)

    Zhang, Ming; Li, Xiaolong; He, Yang; Zhang, Jun; Chen, Zhongyong; Yu, Kexun

    2015-01-01

    Highlights: • We investigate the way to limit the plasma disruption overvoltage by using the MOVs. • An overvoltage model of plasma disruption is introduced. • The overvoltage protection scheme has been verified by disruption experiments. • The overvoltage during plasma disruption can be limited to 330 V. - Abstract: During a plasma disruption the magnetic flux in the tokamak changes rapidly, which in most cases will cause high-voltage surges among the magnetic systems and may bring severe damage to the components if there is no overvoltage protection. This paper investigates the way to limit the plasma disruption overvoltage and absorb the energy with the use of metal oxide varistors (MOVs). An overvoltage model of plasma disruption is introduced which can be used for the simulation of plasma disruption and the analysis of the overvoltage. The effectiveness of the overvoltage protection system is validated with disruption experiments. It shows that by optimizing the varistors voltage, the overvoltage during plasma disruption can be limited to an ideal low value. Now the overvoltage protection system has been deployed in J-TEXT tokamak and serves well for daily experiments.

  2. Fuel disruption mechanisms determined in-pile in the ACRR

    International Nuclear Information System (INIS)

    Wright, S.A.; Fischer, E.A.

    1984-09-01

    Over thirty in-pile experiments were performed to investigate fuel disruption behavior for LMFBR loss of flow (LOF) accidents. These experiments reproduced the heating transients for a variety of accidents ranging from slow LOF accidents to rapid LOF-driven-TOP accidents. In all experiments the timing and mode of the fuel disruption were observed with a high speed camera, enabling detailed comparisons with a fuel pin code, SANDPIN. This code transient intra- and inter-granular fission gas behavior to predict the macroscopic fuel behavior, such as fission gas induced swelling and frothing, cracking and breakup of solid fuel, and fuel vapor pressure driven dispersal. This report reviews the different modes of fuel disruption as seen in the experiments and then describes the mechanism responsible for the disruption. An analysis is presented that describes a set of conditions specifying the mode of fuel disruption and the heating conditions required to produce the disruption. The heating conditions are described in terms of heating rate (K/s), temperature gradient, and fuel temperature. A fuel disruption map is presented which plots heating rate as a function of fuel temperature to illustrate the different criteria for disruption. Although this approach to describing fuel disruption oversimplifies the fission gas processes modeled by SANDPIN, it does illustrate the criteria used to determine which fuel disruption mechanism is dominant and on what major fission gas parameters it depends

  3. 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.

  4. 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.

  5. The disruption management model.

    Science.gov (United States)

    McAlister, James

    2011-10-01

    Within all organisations, business continuity disruptions present a set of dilemmas that managers may not have dealt with before in their normal daily duties. The disruption management model provides a simple but effective management tool to enable crisis management teams to stay focused on recovery in the midst of a business continuity incident. The model has four chronological primary headlines, which steer the team through a quick-time crisis decision-making process. The procedure facilitates timely, systematic, rationalised and justified decisions, which can withstand post-event scrutiny. The disruption management model has been thoroughly tested within an emergency services environment and is proven to significantly support clear and concise decision making in a business continuity context.

  6. 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.

  7. Sustainable Disruption Management

    DEFF Research Database (Denmark)

    Vaaben, Bo Valdemar

    The world we live in is globalized. Goods are seldom made in the place where they are used or consumed, and we do increasingly travel to other countries for either business or pleasure. In our everyday lives we rely on well-functioning global transportations systems to continue the standard...... in the same way, when operation is disrupted. Never the less, we may recall that the Suez Canal was closed due to riots in Egypt, that the fuel price was impacted by threats of closing of the Strait of Hormuz, and we do from time to time hear about acts of piracy outside the coast of Somalia. All...... papers combining disruption management and flight planning through an integrated optimization approach. An additional contribution of the thesis is to show how flexible flight speeds can be used to improve recovery from disruptions, while at the same time allowing an airline to trade off fuel costs...

  8. Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations

    Directory of Open Access Journals (Sweden)

    Kathryn Milligan-Myhre

    2016-02-01

    Full Text Available Animal hosts must co-exist with beneficial microbes while simultaneously being able to mount rapid, non-specific, innate immune responses to pathogenic microbes. How this balance is achieved is not fully understood, and disruption of this relationship can lead to disease. Excessive inflammatory responses to resident microbes are characteristic of certain gastrointestinal pathologies such as inflammatory bowel disease (IBD. The immune dysregulation of IBD has complex genetic underpinnings that cannot be fully recapitulated with single-gene-knockout models. A deeper understanding of the genetic regulation of innate immune responses to resident microbes requires the ability to measure immune responses in the presence and absence of the microbiota using vertebrate models with complex genetic variation. Here, we describe a new gnotobiotic vertebrate model to explore the natural genetic variation that contributes to differences in innate immune responses to microbiota. Threespine stickleback, Gasterosteus aculeatus, has been used to study the developmental genetics of complex traits during the repeated evolution from ancestral oceanic to derived freshwater forms. We established methods to rear germ-free stickleback larvae and gnotobiotic animals monoassociated with single bacterial isolates. We characterized the innate immune response of these fish to resident gut microbes by quantifying the neutrophil cells in conventionally reared monoassociated or germ-free stickleback from both oceanic and freshwater populations grown in a common intermediate salinity environment. We found that oceanic and freshwater fish in the wild and in the laboratory share many intestinal microbial community members. However, oceanic fish mount a strong immune response to residential microbiota, whereas freshwater fish frequently do not. A strong innate immune response was uniformly observed across oceanic families, but this response varied among families of freshwater fish

  9. Endocrine Disrupting Chemicals and Disease Susceptibility

    Science.gov (United States)

    Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

    2011-01-01

    Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

  10. 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

  11. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  12. 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)

  13. Magnetohydrodynamic simulations of density-limit disruptions in tokamaks

    International Nuclear Information System (INIS)

    Kleva, R.G.; Drake, J.F.; Denton, R.E.

    1990-01-01

    Magnetohydrodynamic simulations are presented which demonstrate that density limit disruptions can be triggered by edge radiation which destabilizes a q = 1 kink followed by a q = 2 tearing mode. A bubble of cold plasma is injected from the edge into the center by the q = 1 kink. The q = 2 mode then broadens the current profile and throws the hot plasma to the wall. The MHD simulations presented are the first to successfully reproduce several key features of density limit disruptions including (1) the rapid drop in the central temperature, (2) the rapid expansion of the current profile, (3) the m = 1 cold bubble which is seen to be injected from the edge into the center during density limit disruptions on JET, and (4) disruptions in sawtoothing discharges. (author)

  14. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

  15. Immunity to fish rhabdoviruses

    Science.gov (United States)

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non-virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  16. Immunity to fish rhabdoviruses.

    Science.gov (United States)

    Purcell, Maureen K; Laing, Kerry J; Winton, James R

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non‑virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  17. Immunity to Fish Rhabdoviruses

    Directory of Open Access Journals (Sweden)

    Maureen K. Purcell

    2012-01-01

    Full Text Available Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M protein to mediate host-cell shutoff and the non‑virion (NV protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  18. Emerging and Disruptive Technologies

    OpenAIRE

    Kricka, Larry J.

    2016-01-01

    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 test...

  19. Zinc and immunity: An essential interrelation.

    Science.gov (United States)

    Maares, Maria; Haase, Hajo

    2016-12-01

    The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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...

  1. 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.

  2. [Saccharomyces boulardii modulates dendritic cell properties and intestinal microbiota disruption after antibiotic treatment].

    Science.gov (United States)

    Collignon, A; Sandré, C; Barc, M-C

    2010-09-01

    Saccharomyces boulardii is a non-pathogenic yeast with biotherapeutic properties that has been used successfully to prevent and to treat various infectious and antibiotic-associated diarrheas. The intestinal microbiota is responsible for colonization resistance and immune response to pathogens but can be disrupted by antibiotics and lose its barrier effect. Dendritic cells (DCs) are professional antigen-presenting cells of the immune system with the ability to initiate a primary immune response or immune tolerance. In a human microbiota-associated mouse model, we evaluated the influence of S. boulardii on the composition of the microbiota and on the properties of dendritic cells in normal homeostatic conditions and after antibiotic-induced stress. The DCs were derived from splenic precursors. Membrane antigen expression and phagocytosis of FITC-latex beads by DCs were evaluated by flow cytometry. The molecular analysis of the microbiota was performed with fluorescence in situ hybridization (FISH) combined with flow cytometry or confocal microscopy using group specific 16S rRNA targeted probes. This evaluation was conducted during and after a 7-day oral treatment with amoxicillin-clavulanic acid alone and in combination with the administration of the yeast. The antibiotic treatment increased the phagocytic activity of DCs. Their antigen presenting function (MHC class II antigen and CD 86 costimulatory molecule membrane expression) was up-regulated. This reflects a functional activation of DCs. In the presence of S. boulardii, the modification of membrane antigen expression was down regulated. To correlate these modifications to the microbiota disruption, we analyzed in parallel the composition of the intestinal microbiota. As previously shown, the amoxicillin-clavulanic acid treatment, both alone and with S. boulardii, did not quantitatively alter the total microbiota. In contrast, after one day of the antibiotic treatment the Clostridium coccoides group decreased

  3. Innate immunity

    African Journals Online (AJOL)

    Ronnie Anderson is Director of the Medical Research Council Unit for Inflammation and Immunity. ... field have included macrophage, T cell, cytokine and cytokine activated killer cell interactions .... monocytes, mast cells, lymphocytes, eccrine.

  4. Childhood immunization

    Science.gov (United States)

    Romain, Sandra; Schillaci, Michael A.

    2009-01-01

    ABSTRACT OBJECTIVE To examine childhood immunization levels relative to the number of family physicians, pediatricians, and public health nurses in Ontario. DESIGN Retrospective comparative analysis of publicly available data on immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. SETTING Ontario. PARTICIPANTS Seven-year-old children, family physicians, pediatricians, and public health nurses in Ontario. MAIN OUTCOME MEASURES The association between immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. RESULTS We found correlations between immunization coverage levels and the relative number (ie, per 1000 Ontario residents) of family physicians (ρ = 0.60) and pediatricians (ρ = 0.70) and a lower correlation with the relative number of public health nurses (ρ = 0.40), although none of these correlations was significant. A comparison of temporal trends illustrated that variation in the relative number of family physicians and pediatricians in Ontario was associated with similar variation in immunization coverage levels. CONCLUSION Increasing the number of family physicians and pediatricians might help to boost access to immunizations and perhaps other components of cost-saving childhood preventive care. PMID:19910599

  5. Disruptive Space Technology

    OpenAIRE

    Benson, Jim

    2004-01-01

    In 1997 "The Innovator’s Dilemma" by Clayton M. Christensen became a popular book in the small satellite and launch vehicle communities. But like the weather, every one talks about “Disruptive Technology” but few do anything about it. In the ‘70s and ‘80s, people were looking for “Paradigm Shifts,” and since the resurrection of Donald Rumsfeld, a recent watchword has been “Transformational Technology.” But today’s buzzword is now “Responsive Space Systems.”

  6. 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.

  7. Disruptions in the TFTR tokamak

    International Nuclear Information System (INIS)

    Janos, A.; Fredrickson, E.D.; McGuire, K.; Batha, S.H.; Bell, M.G.; Bitter, M.; Budny, R.; Bush, C.E.; Efthimion, P.C.; Hawryluk, R.J.; Hill, K.W.; Hosea, J.; Jobes, F.C.; Johnson, D.W.; Levinton, F.; Mansfield, D.; Meade, D.; Medley, S.S.; Monticello, D.; Mueller, D.; Nagayama, Y.; Owens, D.K.; Park, H.; Park, W.; Post, D.E.; Schivell, J.; Strachan, J.D.; Taylor, G.; Ulrickson, M.; Goeler, S. von; Wilfrid, E.; Wong, K.L.; Yamada, M.; Young, K.M.; Zarnstorff, M.C.; Zweben, S.J.; Drake, J.F.; Kleva, R.G.; Fleischmann, H.H.

    1993-03-01

    For a successful reactor, it will be useful to predict the occurrence of disruptions and to understand disruption effects including how a plasma disrupts onto the wall and how reproducibly it does so. Studies of disruptions on TFTR at both high-β pol and high-density have shown that, in both types, a fast growing m/n=1/1 mode plays an important role. In highdensity disruptions, a newly observed fast m/n = 1/1 mode occurs early in the thermal decay phase. For the first time in TFTR q-profile measurements just prior to disruptions have been made. Experimental studies of heat deposition patterns on the first wall of TFTR due to disruptions have provided information on MHD phenomena prior to or during the disruption, how the energy is released to the wall, and the reproducibility of the heat loads from disruptions. This information is important in the design of future devices such as ITER. Several new processes of runaway electron generation are theoretically suggested and their application to TFTR and ITER is considered, together with a preliminary assessment of x-ray data from runaways generated during disruptions

  8. The location of splenic NKT cells favours their rapid activation by blood-borne antigen.

    Science.gov (United States)

    Barral, Patricia; Sánchez-Niño, María Dolores; van Rooijen, Nico; Cerundolo, Vincenzo; Batista, Facundo D

    2012-05-16

    Natural killer T (NKT) cells play an important role in mounting protective responses to blood-borne infections. However, though the spleen is the largest blood filter in the body, the distribution and dynamics of NKT cells within this organ are not well characterized. Here we show that the majority of NKT cells patrol around the marginal zone (MZ) and red pulp (RP) of the spleen. In response to lipid antigen, these NKT cells become arrested and rapidly produce cytokines, while the small proportion of NKT cells located in the white pulp (WP) exhibit limited activation. Importantly, disruption of the splenic MZ by chemical or genetic approaches results in a severe reduction in NKT cell activation indicating the need of cooperation between both MZ macrophages and dendritic cells for efficient NKT cell responses. Thus, the location of splenic NKT cells in the MZ and RP facilitates their access to blood-borne antigen and enables the rapid initiation of protective immune responses.

  9. 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.

  10. Disruptions in DIII-D

    International Nuclear Information System (INIS)

    Reiman, A.; Taylor, P.; Kellman, A.; LaHaye, R.

    1996-01-01

    We report on the results of a statistical analysis of the DIII-D disruption data base, and on an examination of a selected subset of the shots to determine the likely causes of disruptions. The statistical analysis focuses on the dependence of the disruption rate on key dimensionless parameters. We find that the disruption frequency is high at modest values of the parameters, and that it can be relatively low at operational limits. For example, the disruption frequency in an ITER relevant regime (β N /l i ∼ 2, 3 G > 0.6, where n G is the Greenwald limit) is approximately 23%. For this range of q, the disruption frequency rises only modestly to about 35% at the β limit, consistent with previous observations of a soft β limit for this q regime. For the range 6 95 G G < .9) in all q regimes we have studied. The location of the minimum moves to higher density with increasing q

  11. Circadian Disruption Changes Gut Microbiome Taxa and Functional Gene Composition.

    Science.gov (United States)

    Deaver, Jessica A; Eum, Sung Y; Toborek, Michal

    2018-01-01

    Disrupted circadian rhythms and alterations of the gut microbiome composition were proposed to affect host health. Therefore, the aim of this research was to identify whether these events are connected and if circadian rhythm disruption by abnormal light-dark (LD) cycles affects microbial community gene expression and host vulnerability to intestinal dysfunction. Mice were subjected to either a 4-week period of constant 24-h light or of normal 12-h LD cycles. Stool samples were collected at the beginning and after the circadian rhythm disruption. A metatranscriptomic analysis revealed an increase in Ruminococcus torques , a bacterial species known to decrease gut barrier integrity, and a decrease in Lactobacillus johnsonii , a bacterium that helps maintain the intestinal epithelial cell layer, after circadian rhythm disruption. In addition, genes involved in pathways promoting host beneficial immune responses were downregulated, while genes involved in the synthesis and transportation of the endotoxin lipopolysaccharide were upregulated in mice with disrupted circadian cycles. Importantly, these mice were also more prone to dysfunction of the intestinal barrier. These results further elucidate the impact of light-cycle disruption on the gut microbiome and its connection with increased incidence of disease in response to circadian rhythm disturbances.

  12. 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

  13. 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...... of family members in social historical contexts. Studying the multiple perspectives of family members shows how social support conceptualized as care practises is conflictual in the changing everyday family practices that are transformed by policy. The purpose of studying how families manage to flee civil...... 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....

  14. Immune System

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  15. Immunizing Adults

    Centers for Disease Control (CDC) Podcasts

    Vaccines aren’t just for kids; adults also need to get immunized. Overall, far too many people 19 years and older aren’t getting the vaccines they need and remain unprotected. In this podcast, Dr. Walter Williams discuss the importance of adults being fully vaccinated.

  16. Disruptive Technology: An Uncertain Future

    Science.gov (United States)

    2005-05-21

    Technology that overturns market -- Military - Technology that causes a fundamental change in force structure, basing, and capability balance * Disruptive Technologies may arise from systems or enabling technology.

  17. Major disruption process in tokamak

    International Nuclear Information System (INIS)

    Kurita, Gen-ichi; Azumi, Masafumi; Tuda, Takashi; Takizuka, Tomonori; Tsunematsu, Toshihide; Tokuda, Shinji; Itoh, Kimitaka; Takeda, Tatsuoki

    1981-11-01

    The major disruption in a cylindrical tokamak is investigated by using the multi-helicity code, and the destabilization of the 3/2 mode by the mode coupling with the 2/1 mode is confirmed. The evolution of the magnetic field topology caused by the major disruption is studied in detail. The effect of the internal disruption on the 2/1 magnetic island width is also studied. The 2/1 magnetic island is not enhanced by the flattening of the q-profile due to the internal disruption. (author)

  18. 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.

  19. Rapid single-step methods for detection of two immune defence gene polymorphisms: the myeloperoxidase (MPO) G-129A and the Fc gamma receptor 2A (FCGR2A) H/R131

    DEFF Research Database (Denmark)

    Mølle, Ingolf; Melsvik, Dorte; Østergaard, Mette

    2007-01-01

    Polymorphisms of immune defence genes may act as disease modifiers and are studied by many researchers. A conclusive analysis of the impact of genetic variations typically requires a large number of sample specimens, and in retrospective studies this may include samples of reduced quality, e.g. f...

  20. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  1. Disruption, vertical displacement event and halo current characterization for ITER

    International Nuclear Information System (INIS)

    Wesley, J.; Fujisawa, N.; Ortolani, S.; Putvinski, S.; Rosenbluth, M.N.

    1997-01-01

    Characteristics, in ITER, of plasma disruptions, vertical displacement events (VDEs) and the conversion of plasma current to runaway electron current in a disruption are presented. In addition to the well known potential of disruptions to produce rapid thermal energy and plasma current quenches and theoretical predictions that show the likelihood of ∼ 50% runaway conversion, an assessment of VDE and halo current characteristics in vertically elongated tokamaks shows that disruptions in ITER will result in VDEs with peak in-vessel halo currents of up to 50% of the predisruption plasma current and with toroidal peaking factors (peak/average current density) of up to 4:1. However, the assessment also shows an inverse correlation between the halo current magnitude and the toroidal peaking factor; hence, ITER VDEs can be expected to have a product of normalized halo current magnitude times toroidal peaking factor of ≤ 75%. (author). 3 refs, 2 figs, 3 tabs

  2. Tokamak plasma current disruption infrared control system

    International Nuclear Information System (INIS)

    Kugel, H.W.; Ulrickson, M.

    1987-01-01

    This patent describes a device for magnetically confining a plasma driven by a plasma current and contained within a toroidal vacuum chamber, the device having an inner toroidal limiter on an inside wall of the vacuum chamber and an arrangement for the rapid prediction and control in real time of a major plasma disruption. The arrangement is described which includes: scanning means sensitive to infrared radiation emanating from within the vacuum chamber, the infrared radiation indicating the temperature along a vertical profile of the inner toroidal limiter. The scanning means is arranged to observe the infrared radiation and to produce in response thereto an electrical scanning output signal representative of a time scan of temperature along the vertical profile; detection means for analyzing the scanning output signal to detect a first peaked temperature excursion occurring along the profile of the inner toroidal limiter, and to produce a detection output signal in repsonse thereto, the detection output signal indicating a real time prediction of a subsequent major plasma disruption; and plasma current reduction means for reducing the plasma current driving the plasma, in response to the detection output signal and in anticipation of a subsequent major plasma disruption

  3. NIH Common Fund - Disruptive Proteomics Technologies - Challenges and Opportunities | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    This Request for Information (RFI) is directed toward determining how best to accelerate research in disruptive proteomics technologies. The Disruptive Proteomics Technologies (DPT) Working Group of the NIH Common Fund wishes to identify gaps and opportunities in current technologies and methodologies related to proteome-wide measurements.  For the purposes of this RFI, “disruptive” is defined as very rapid, very significant gains, similar to the "disruptive" technology development that occurred in DNA sequencing technology.

  4. Social media disruptive change in healthcare : Responses of healthcare providers?

    NARCIS (Netherlands)

    Smailhodzic, E.; Boonstra, A.; Langley, D.J.

    2016-01-01

    Social media represent specific types of technologies that are end-user driven and end-users are able to drive disruptive change giving little time to organizations to react. With rapid and powerful emergence of social media communities in healthcare, this sector is faced with new and alternative

  5. Social media disruptive change in healthcare : responses of healthcare providers

    NARCIS (Netherlands)

    Smailhodzic, Edin; Boonstra, Albert; Langley, David

    Social media represent specific types of technologies that are end-user driven and end-users are able to drive disruptive change giving little time to organizations to react. With rapid and powerful emergence of social media communities in healthcare, this sector is faced with new and alternative

  6. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  7. Visual observations of fuel disruption in in-pile LMFBR accident experiments

    International Nuclear Information System (INIS)

    Wright, S.A.; Mast, P.K.

    1982-01-01

    Sandia National Laboratories has been investigating initiation phase phenomena in a series of Fuel Disruption (FD) experiments since 1977. In this program high speed cinematography is used to observe fuel disruption in in-pile experiments that simulate loss of flow accidents. Thus, these experiments provide high resolution measurements of initial fuel and clad motion with prototypic materials and prototypic heating conditions. The main objective of the FD experiment is to determine the timing (relative to fuel temperature) and the mode of fuel disruption under LOF heating conditions. Observed modes of disruption include fuel swelling, solid state breakup, cracking, ejection of a molten fuel jet, slumping, and rapid expansion of small particles. Because the temperature and character of the fuel at disruption are known, disruption can be correlated with the mechanisms driving the disruption such as fuel vapor pressure, molten fuel expansion, fission gases, and impurity gases

  8. 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.

  9. The cytoskeleton is disrupted by the bacterial effector HrpZ, but not by the bacterial PAMP flg22, in tobacco BY-2 cells.

    Science.gov (United States)

    Guan, Xin; Buchholz, Günther; Nick, Peter

    2013-04-01

    Plant innate immunity is composed of two layers. Basal immunity is triggered by pathogen-associated molecular patterns (PAMPs) such as the flagellin-peptide flg22 and is termed PAMP-triggered immunity (PTI). In addition, effector-triggered immunity (ETI) linked with programmed cell death and cytoskeletal reorganization can be induced by pathogen-derived factors, such as the Harpin proteins originating from phytopathogenic bacteria. To get insight into the link between cytoskeleton and PTI or ETI, this study followed the responses of actin filaments and microtubules to flg22 and HrpZ in vivo by spinning-disc confocal microscopy in GFP-tagged marker lines of tobacco BY-2. At a concentration that clearly impairs mitosis, flg22 can induce only subtle cytoskeletal responses. In contrast, HrpZ causes a rapid and massive bundling of actin microfilaments (completed in ~20 min, i.e. almost simultaneously with extracellular alkalinization), which is followed by progressive disintegration of actin cables and cytoplasmic microtubules, a loss of cytoplasmic structure, and vacuolar disintegration. Cytoskeletal disruption is proposed as an early event that discriminates HrpZ-triggered ETI-like defence from flg22-triggered PTI.

  10. Immunizations for Preterm Babies

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations For Preterm Babies Safety & ...

  11. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  12. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  13. Supplementation with a fish oil-enriched, high-protein medical food leads to rapid incorporation of EPA into white blood cells and modulates immune responses within one week in healthy men and women.

    Science.gov (United States)

    Faber, Joyce; Berkhout, Marloes; Vos, Arjan P; Sijben, John W C; Calder, Philip C; Garssen, Johan; van Helvoort, Ardy

    2011-05-01

    Immune modulatory effects of EPA and DHA are well described. However, these fatty acids must be effectively incorporated into cell membrane phospholipids to modify cell function. To address the absence of human data regarding short-term incorporation, the present study investigated the incorporation of EPA and DHA into white blood cells (WBC) at different time points during 1 wk of supplementation with a medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides. Additionally, the effects on ex vivo immune function were determined. In a single-arm, open label study, 12 healthy men and women consumed 2 × 200 mL of medical food providing 2.4 g EPA, 1.2 g DHA, 39.7 g protein (including 4.4 g L-leucine), and 5.6 g oligosaccharides daily. Blood samples were taken at d 0 (baseline), 1, 2, 4, and 7. Within 1 d of nutritional intervention, the percentage of EPA in phospholipids of WBC increased from 0.5% at baseline to 1.3% (P blood cultures was significantly increased within 1 wk. Nutritional supplementation with a fish oil-enriched medical food significantly increased the percentage of EPA in phospholipids of WBC within 1 wk. Simultaneously, ex vivo immune responsiveness to LPS increased significantly. These results hold promise for novel applications such as fast-acting nutritional interventions in cancer patients, which should be investigated in future studies.

  14. Quantitative Methods for Measuring Repair Rates and Innate-Immune Cell Responses in Wounded Mouse Skin

    Directory of Open Access Journals (Sweden)

    Zhi Li

    2018-02-01

    Full Text Available In skin wounds, innate-immune cells clear up tissue debris and microbial contamination, and also secrete cytokines and other growth factors that impact repair process such as re-epithelialization and wound closure. After injury, there is a rapid influx and efflux of immune cells at wound sites, yet the function of each innate cell population in skin repair is still under investigation. Flow cytometry is a valuable research tool for detecting and quantifying immune cells; however, in mouse back skin, the difficulty in extracting immune cells from small area of skin due to tissue complexity has made cytometric analysis an underutilized tool. In this paper, we provide detailed methods on the digestion of lesion-specific skin without disrupting antigen expression followed by multiplex cell staining that allows for identification of seven innate-immune populations, including rare subsets such as group-3 innate lymphoid cells (ILC3s, by flow-cytometry analysis. Furthermore, when studying the functions of immune cells to tissue repair an important metric to monitor is size of the wound opening. Normal wounds close steadily albeit at non-linear rates, while slow or stalled wound closure can indicate an underlying problem with the repair process. Calliper measurements are difficult and time-consuming to obtain and can require repeated sedation of experimental animals. We provide advanced methods for measuring of wound openness; digital 3D image capture and semi-automated image processing that allows for unbiased, reliable measurements that can be taken repeatedly over time.

  15. Toward Improved Parenting Interventions for Disruptive Child Behavior : Engaging Disadvantaged Families and Searching for Effective Elements

    NARCIS (Netherlands)

    Leijten, P.H.O.

    2014-01-01

    Parenting interventions are a promising strategy to prevent antisocial behavior in society. Evidence accumulates that parenting interventions can reduce disruptive child behavior, and insight rapidly increases into which families they benefit most. At the same time, however, several high risk

  16. 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.

  17. 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.

  18. When Disruptive Approaches Meet Disruptive Technologies: Learning at a Distance.

    Science.gov (United States)

    Gibson, Chere Campbell

    2000-01-01

    Reviews research on constructivism in learning and selection of learning strategies. Suggests linking constructivism with instructional technologies for continuing medical education in order to "disrupt" reactive, habitual ways of learning and encourage active engagement. (SK)

  19. Plasma disruption modeling and simulation

    International Nuclear Information System (INIS)

    Hassanein, A.

    1994-01-01

    Disruptions in tokamak reactors are considered a limiting factor to successful operation and reliable design. The behavior of plasma-facing components during a disruption is critical to the overall integrity of the reactor. Erosion of plasma facing-material (PFM) surfaces due to thermal energy dump during the disruption can severely limit the lifetime of these components and thus diminish the economic feasibility of the reactor. A comprehensive understanding of the interplay of various physical processes during a disruption is essential for determining component lifetime and potentially improving the performance of such components. There are three principal stages in modeling the behavior of PFM during a disruption. Initially, the incident plasma particles will deposit their energy directly on the PFM surface, heating it to a very high temperature where ablation occurs. Models for plasma-material interactions have been developed and used to predict material thermal evolution during the disruption. Within a few microseconds after the start of the disruption, enough material is vaporized to intercept most of the incoming plasma particles. Models for plasma-vapor interactions are necessary to predict vapor cloud expansion and hydrodynamics. Continuous heating of the vapor cloud above the material surface by the incident plasma particles will excite, ionize, and cause vapor atoms to emit thermal radiation. Accurate models for radiation transport in the vapor are essential for calculating the net radiated flux to the material surface which determines the final erosion thickness and consequently component lifetime. A comprehensive model that takes into account various stages of plasma-material interaction has been developed and used to predict erosion rates during reactor disruption, as well during induced disruption in laboratory experiments

  20. Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-α Release by Mononuclear Cells in Healthy Adults

    NARCIS (Netherlands)

    Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; Vos, de Alex F.; Vos, de Willem M.; Poll, van der Tom; Wiersinga, W.J.

    2016-01-01

    Objectives:Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,

  1. Symposium on disruptive instabilities at Garching

    International Nuclear Information System (INIS)

    Lackner, K.

    1979-01-01

    The phenomenon of disruptive instabilities was investigated with a special care at the IPP at Garching. After lectures and panel sessions it appears suitable, to subdivide the disruptive phenomena into four classes: 1. The internal disruption (the socalled saw-tooth oscillators). 2. the socalled reconnection disruptions. 3. The large disruptions. 4. The small disruptions. The four appearance forms of the phenomena are briefly explained. (GG) [de

  2. Epicutaneous Immunization with Type II Collagen Inhibits both Onset and Progression of Chronic Collagen-Induced Arthritis

    OpenAIRE

    Strid, Jessica; Tan, Lee Aun; Strobel, Stephan; Londei, Marco; Callard, Robin

    2007-01-01

    Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inh...

  3. 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...

  4. Integrated Circuit Immunity

    Science.gov (United States)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  5. DISRUPTIVE TECHNOLOGIES: AN EXPANDED VIEW

    OpenAIRE

    JAMES M. UTTERBACK; HAPPY J. ACEE

    2005-01-01

    The term "disruptive technology" as coined by Christensen (1997, The Innovator's Dilemma; How New Technologies Cause Great Firms to Fail. Harvard Business School Press) refers to a new technology having lower cost and performance measured by traditional criteria, but having higher ancillary performance. Christensen finds that disruptive technologies may enter and expand emerging market niches, improving with time and ultimately attacking established products in their traditional markets. This...

  6. Improvements in disruption prediction at ASDEX Upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Aledda, R., E-mail: raffaele.aledda@diee.unica.it; Cannas, B., E-mail: cannas@diee.unica.it; Fanni, A., E-mail: fanni@diee.unica.it; Pau, A., E-mail: alessandro.pau@diee.unica.it; Sias, G., E-mail: giuliana.sias@diee.unica.it

    2015-10-15

    Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

  7. Improvements in disruption prediction at ASDEX Upgrade

    International Nuclear Information System (INIS)

    Aledda, R.; Cannas, B.; Fanni, A.; Pau, A.; Sias, G.

    2015-01-01

    Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

  8. Immune function in arctic mammals

    DEFF Research Database (Denmark)

    Desforges, Jean-Pierre; Jasperse, Lindsay; Jensen, Trine Hammer

    2018-01-01

    Natural killer (NK) cells are a vital part of the rapid and non-specific immune defense against invading pathogens and tumor cells. This study evaluated NK cell-like activity by flow cytometry for the first time in three ecologically and culturally important Arctic mammal species: polar bear (Ursus...... the effector:target cell ratio increased. Comparing NK activity between fresh and cryopreserved mouse lymphocytes revealed little to no difference in function, highlighting the applicability of cryopreserving cells in field studies. The evaluation of this important innate immune function in Arctic mammals can...... contribute to future population health assessments, especially as pollution-induced suppression of immune function may increase infectious disease susceptibility....

  9. Tidal disruption of fuzzy dark matter subhalo cores

    Science.gov (United States)

    Du, Xiaolong; Schwabe, Bodo; Niemeyer, Jens C.; Bürger, David

    2018-03-01

    We study tidal stripping of fuzzy dark matter (FDM) subhalo cores using simulations of the Schrödinger-Poisson equations and analyze the dynamics of tidal disruption, highlighting the differences with standard cold dark matter. Mass loss outside of the tidal radius forces the core to relax into a less compact configuration, lowering the tidal radius. As the characteristic radius of a solitonic core scales inversely with its mass, tidal stripping results in a runaway effect and rapid tidal disruption of the core once its central density drops below 4.5 times the average density of the host within the orbital radius. Additionally, we find that the core is deformed into a tidally locked ellipsoid with increasing eccentricities until it is completely disrupted. Using the core mass loss rate, we compute the minimum mass of cores that can survive several orbits for different FDM particle masses and compare it with observed masses of satellite galaxies in the Milky Way.

  10. A new approach for disruption management in airline operations control

    CERN Document Server

    Castro, António J M; Oliveira, Eugénio

    2014-01-01

    Most of the research efforts dealing with airline scheduling have been done on off-line plan optimization.  However, nowadays, with the increasingly complex and huge traffic at airports, the real challenge is how to react to unexpected events that may cause plan-disruptions, leading to flight delays. Moreover these disruptive events usually affect at least three different dimensions of the situation: the aircraft assigned to the flight, the crew assignment and, often forgotten, the passengers’ journey and satisfaction. This book includes answers to this challenge and proposes the use of the Multi-agent System paradigm to rapidly compose a multi-faceted solution to the disruptive event taking into consideration possible preferences of those three key aspects of the problem. Negotiation protocols taking place between agents that are experts in solving the different problem dimensions, combination of different utility functions and, not less important, the inclusion of the human in the automatic decision-maki...

  11. Population growth changes targets for immunization.

    Science.gov (United States)

    Tuljapurkar, S; John, A M

    1995-01-01

    The faster the rate of population growth in developing countries, the less likely it is that current protocols for immunization against measles, rubella, and mumps will eradicate these childhood diseases. Standard protocols (timing, percentage of children to be immunized) do not take into account the rapid rates of population growth in developing countries (3.0% per year on average in sub-Saharan Africa and 2.0% in the rest of Africa, in Latin America, and in Asia, excluding China). Most public health planning models in this area were created based on static infant populations. The World Health Organization advises vaccinating at least 85% of children aged 6 to 9 months, a 3-month immunization window during which maternal antibodies are low (so the vaccination takes) and herd immunity is high (the probability that a child will encounter the disease is low because most children have been immunized). In practice, the immunization window in developing countries is 1 year or more. More susceptible children are present than assumed by the models. A larger number of susceptible babies are added each year during rapid population growth. As the age range for immunization widens, a higher percentage of children must be vaccinated to eradicate disease (chart). The proportion of each birth cohort that must be immunized rises as the population growth rate increases. At zero population growth, 94% must be vaccinated; at population growth rates greater than 3%, 98% must be vaccinated.

  12. The Pursuit of Profit or Prestige: What the Diffusion of MOOCs Can Tell Us about Disruptive Innovation in US Higher Education

    Science.gov (United States)

    Pheatt, Lara E.

    2017-01-01

    Disruptive innovations are used to lower costs and augment access to high-quality, affordable higher education, but little systematic research is available on the topic. Higher education institutions use disruptive innovations to save students time and money. To understand the process of disruptive innovation, I investigated the rapid diffusion of…

  13. 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

  14. 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

  15. Disruption studies in ASDEX Upgrade

    International Nuclear Information System (INIS)

    Pautasso, G.

    2002-01-01

    Disruption generate large thermal and mechanical stresses on the tokamak components. 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. The study of disruptions on ASDEX Upgrade is focused on these subjects, namely on: (1) understanding the physical mechanisms leading to this phenomenon and learning to avoid it or to predict its occurrence (with neural networks, for example) 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 to dimension or reinforce the machine components to withstand these loads and to extrapolate them to tokamaks still in the design phase; (3) learning to mitigate the consequence of disruptions. (author)

  16. Immune System Quiz

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

  17. Immunization Schedules for Adults

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Adults (19 Years of Age and ... diseases that can be prevented by vaccines . 2018 Immunization Schedule Recommended Vaccinations for Adults by Age and ...

  18. Immunizations and African Americans

    Science.gov (United States)

    ... Data > Minority Population Profiles > Black/African American > Immunizations Immunizations and African Americans African American adults are less ... 19 to 35 months had comparable rates of immunization. African American women are as likely to have ...

  19. Instant Childhood Immunization Schedule

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  20. Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.

    Science.gov (United States)

    Rai, Ashim; Pathak, Divya; Thakur, Shreyasi; Singh, Shampa; Dubey, Alok Kumar; Mallik, Roop

    2016-02-11

    Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. T cell immunity

    OpenAIRE

    Emel Bülbül Başkan

    2013-01-01

    Since birth, our immune system is constantly bombarded with self-antigens and foreign pathogens. To stay healthy, complex immune strategies have evolved in our immune system to maintain self-tolerance and to defend against foreign pathogens. Effector T cells are the key players in steering the immune responses to execute immune functions. While effector T cells were initially identified to be immune promoting, recent studies unraveled negative regulatory functions of effector T cells...

  2. TAD disruption as oncogenic driver.

    Science.gov (United States)

    Valton, Anne-Laure; Dekker, Job

    2016-02-01

    Topologically Associating Domains (TADs) are conserved during evolution and play roles in guiding and constraining long-range regulation of gene expression. Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. One mechanism locally disrupts domains by deleting or mutating a TAD boundary leading to fusion of the two adjacent TADs. The other mechanism involves genomic rearrangements that break up TADs and creates new ones without directly affecting TAD boundaries. Understanding the mechanisms by which TADs form and control long-range chromatin interactions will therefore not only provide insights into the mechanism of gene regulation in general, but will also reveal how genomic rearrangements and mutations in cancer genomes can lead to misregulation of oncogenes and tumor suppressors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Immunization Action Coalition

    Science.gov (United States)

    ... IAC | Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Favorites ACIP Recommendations Package Inserts Additional Immunization Resources Photos Adult Vaccination Screening Checklists Ask the ...

  4. Just one look: Direct gaze briefly disrupts visual working memory.

    Science.gov (United States)

    Wang, J Jessica; Apperly, Ian A

    2017-04-01

    Direct gaze is a salient social cue that affords rapid detection. A body of research suggests that direct gaze enhances performance on memory tasks (e.g., Hood, Macrae, Cole-Davies, & Dias, Developmental Science, 1, 67-71, 2003). Nonetheless, other studies highlight the disruptive effect direct gaze has on concurrent cognitive processes (e.g., Conty, Gimmig, Belletier, George, & Huguet, Cognition, 115(1), 133-139, 2010). This discrepancy raises questions about the effects direct gaze may have on concurrent memory tasks. We addressed this topic by employing a change detection paradigm, where participants retained information about the color of small sets of agents. Experiment 1 revealed that, despite the irrelevance of the agents' eye gaze to the memory task at hand, participants were worse at detecting changes when the agents looked directly at them compared to when the agents looked away. Experiment 2 showed that the disruptive effect was relatively short-lived. Prolonged presentation of direct gaze led to recovery from the initial disruption, rather than a sustained disruption on change detection performance. The present study provides the first evidence that direct gaze impairs visual working memory with a rapidly-developing yet short-lived effect even when there is no need to attend to agents' gaze.

  5. Trauma equals danger—damage control by the immune system

    Science.gov (United States)

    Stoecklein, Veit M.; Osuka, Akinori; Lederer, James A.

    2012-01-01

    Traumatic injuries induce a complex host response that disrupts immune system homeostasis and predisposes patients to opportunistic infections and inflammatory complications. The response to injuries varies considerably by type and severity, as well as by individual variables, such as age, sex, and genetics. These variables make studying the impact of trauma on the immune system challenging. Nevertheless, advances have been made in understanding how injuries influence immune system function as well as the immune cells and pathways involved in regulating the response to injuries. This review provides an overview of current knowledge about how traumatic injuries affect immune system phenotype and function. We discuss the current ideas that traumatic injuries induce a unique type of a response that may be triggered by a combination of endogenous danger signals, including alarmins, DAMPs, self-antigens, and cytokines. Additionally, we review and propose strategies for redirecting injury responses to help restore immune system homeostasis. PMID:22654121

  6. MANAGING DISRUPTIVE BEHAVIOR OF STUDENTS IN LANGUAGE CLASSROOM

    Directory of Open Access Journals (Sweden)

    Siti Khasinah

    2017-05-01

    Full Text Available This article describes students’ disruptive behaviors in language classroom that may greatly affect language teaching and learning process, especially in ESL or EFL classes. Teachers should know what disruptive behavior is to enable them to deal with problems occurred in their classroom or to take preventive actions to keep their students well-behaved during the class. This can reduce the occurrence of misbehavior of students in their classroom. To prevent disruption in the classroom, teachers should establish behavioral expectations in the first day of the semester and the expectations can be based on students attendance, arrivals and departures, class participation, full English speaking, and other appropriate conducts in the syllabus and discuss them at the outset of the term. The agreement is then assigned as a learning contract or a code of conducts with which bounds the whole class. Consequently, whenever students are misbehaved, teachers and other students will directly know and recognize that the behaviors are out of the code. There are factors reasoning students to behave badly, so teachers as trouble solvers have to find appropriate strategies that are effective in helping students keep the code. Otherwise, the disruptions will escalate quickly and the problems will increase in numbers rapidly and finally, teachers will have to work very hard to avoid teaching failure and “losing face” when they cannot manage the disruption as listed in the expectation.

  7. Initiation of innate immune responses by surveillance of homeostasis perturbations.

    Science.gov (United States)

    Colaço, Henrique G; Moita, Luis F

    2016-07-01

    Pathogen recognition, signaling transduction pathways, and effector mechanisms are necessary steps of innate immune responses that play key roles in the early phase of defense and in the stimulation of the later specific response of adaptive immunity. Here, we argue that in addition to the direct recognition of conserved common structural and functional molecular signatures of microorganisms using pattern recognition receptors, hosts can mount an immune response following the sensing of disruption in homeostasis as proximal reporters for infections. Surveillance of disruption of core cellular activities leading to defense responses is a flexible strategy that requires few additional components and that can effectively detect relevant threats. It is likely to be evolutionarily very conserved and ancient because it is operational in organisms that lack pattern recognition triggered immunity. A homeostasis disruption model of immune response initiation and modulation has broad implications for pathophysiology and treatment of disease and might constitute an often overlooked but central component of a comprehensive conceptual framework for innate immunity. © 2016 Federation of European Biochemical Societies.

  8. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

    DEFF Research Database (Denmark)

    Ecker, Simone; Chen, Lu; Pancaldi, Vera

    2017-01-01

    Background: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results: We apply a novel analytical approach to measure and compare transcriptional and epigenetic v...

  9. Disruptive Technologies in Higher Education

    Science.gov (United States)

    Flavin, Michael

    2012-01-01

    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…

  10. 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)

  11. Disruptive Pupils and Teacher Stress.

    Science.gov (United States)

    Dunham, Jack

    1981-01-01

    Teachers have identified a number of stress situations in their work with disruptive children: insecurity due to student unpredictability, doubting their effectiveness, frustrated attempts at communication with other professionals, and feelings of isolation and limited social relationships (expressed by residential workers). (CT)

  12. 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

  13. 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)

  14. 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)

  15. 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.

  16. 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

  17. Survey of disruption causes at JET

    International Nuclear Information System (INIS)

    De Vries, P.C.; Johnson, M.F.; Alper, B.; Hender, T.C.; Riccardo, V.; Buratti, P.; Koslowski, H.R.

    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 effort to avoid or prevent JET disruptions to be more efficient and effective. As expected, a highly complex pattern of chain of events that led to disruptions emerged. It was found that the majority of disruptions had a technical root cause, for example due to control errors, or operator mistakes. These bring a random, non-physics, factor into the occurrence of disruptions and the disruption rate or disruptivity of a scenario may depend more on technical performance than on physics stability issues. The main root cause of JET disruptions was nevertheless due to neo-classical tearing modes that locked, closely followed in second place by disruptions due to human error. The development of more robust operational scenarios has reduced the JET disruption rate over the last decade from about 15% to below 4%. A fraction of all disruptions was caused by very fast, precursorless unpredictable events. The occurrence of these disruptions may set a lower limit of 0.4% to the disruption rate of JET. If one considers on top of that human error and all unforeseen failures of heating or control systems this lower limit may rise to 1.0% or 1.6%, respectively.

  18. Strengthening health system to improve immunization for migrants in China.

    Science.gov (United States)

    Fang, Hai; Yang, Li; Zhang, Huyang; Li, Chenyang; Wen, Liankui; Sun, Li; Hanson, Kara; Meng, Qingyue

    2017-07-01

    Immunization is the most cost-effective method to prevent and control vaccine-preventable diseases. Migrant population in China has been rising rapidly, and their immunization status is poor. China has tried various strategies to strengthen its health system, which has significantly improved immunization for migrants. This study applied a qualitative retrospective review method aiming to collect, analyze and synthesize health system strengthening experiences and practices about improving immunizations for migrants in China. A conceptual framework of Theory of Change was used to extract the searched literatures. 11 searched literatures and 4 national laws and policies related to immunizations for migrant children were carefully studied. China mainly employed 3 health system strengthening strategies to significantly improve immunization for migrant population: stop charging immunization fees or immunization insurance, manage immunization certificates well, and pay extra attentions on immunization for special children including migrant children. These health system strengthening strategies were very effective, and searched literatures show that up-to-date and age-appropriate immunization rates were significantly improved for migrant children. Economic development led to higher migrant population in China, but immunization for migrants, particularly migrant children, were poor. Fortunately various health system strengthening strategies were employed to improve immunization for migrants in China and they were rather successful. The experiences and lessons of immunization for migrant population in China might be helpful for other developing countries with a large number of migrant population.

  19. Our Immune System

    Science.gov (United States)

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  20. Structured Literature Review of digital disruption literature

    DEFF Research Database (Denmark)

    Vesti, Helle; Rosenstand, Claus Andreas Foss; Gertsen, Frank

    2018-01-01

    Digital disruption is a term/phenomenon frequently appearing in innovation management literature. However, no academic consensus exists as to what it entails; conceptual nor theoretical. We use the SLR-method (Structured Literature Review) to investigate digital disruption literature. A SLR......-study conducted in 2017 revealed some useful information on how disruption and digital disruption literature has developed over a specific period. However, this study was less representative of papers addressing digital disruption; which is the in-depth subject of this paper. To accommodate this, we intend...... to conduct a similar SLR-study assembling a body literature having digital disruption as the only common denominator...

  1. [The role of the innate immune system in atopic dermatitis].

    Science.gov (United States)

    Volz, T; Kaesler, S; Skabytska, Y; Biedermann, T

    2015-02-01

    The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

  2. Disruptive technologies and transportation : final report.

    Science.gov (United States)

    2016-06-01

    Disruptive technologies refer to innovations that, at first, may be considered unproven, lacking refinement, relatively unknown, or even impractical, but ultimately they supplant existing technologies and/or applications. In general, disruptive techn...

  3. Disrupting reconsolidation: pharmacological and behavioral manipulations

    NARCIS (Netherlands)

    Soeter, M.; Kindt, M.

    2011-01-01

    We previously demonstrated that disrupting reconsolidation by pharmacological manipulations "deleted" the emotional expression of a fear memory in humans. If we are to target reconsolidation in patients with anxiety disorders, the disruption of reconsolidation should produce content-limited

  4. 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.

  5. 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.

  6. Disruptive technologies - widening the scope -

    OpenAIRE

    Ruhlig, Klaus; Wiemken, Uwe

    2006-01-01

    The term „disruptive technologies” was introduced 1997 by Clayton Christensen in the context of innovations in the business world based upon technological developments. It was meant to sharpen the view for new technologies which can „disrupt” the economic context of a business. Since then it inspired other communities like so many terms in English (or American) language. One of these is the domain of international Research & Technology (R&T) cooperation and technological forecasting for publi...

  7. 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

  8. Biosensor discovery of thyroxine transport disrupting chemicals

    International Nuclear Information System (INIS)

    Marchesini, Gerardo R.; Meimaridou, Anastasia; Haasnoot, Willem; Meulenberg, Eline; Albertus, Faywell; Mizuguchi, Mineyuki; Takeuchi, Makoto; Irth, Hubertus; Murk, Albertinka 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 inhibition assays using the main thyroid hormone transport proteins, T4 binding globulin (TBG) and transthyretin (TTR), in combination with a T4-coated biosensor chip were optimized and automated for screening chemical libraries. The transport protein-based biosensor assays were rapid, high throughput and bioeffect-related. A library of 62 chemicals including the natural hormones, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and metabolites, halogenated bisphenol A (BPA), halogenated phenols, pharmaceuticals, pesticides and other potential environmentally relevant chemicals was tested with the two assays. We discovered ten new active compounds with moderate to high affinity for TBG with the TBG assay. Strikingly, the most potent binding was observed with hydroxylated metabolites of the brominated diphenyl ethers (BDEs) BDE 47, BDE 49 and BDE 99, that are commonly found in human plasma. The TTR assay confirmed the activity of previously identified hydroxylated metabolites of PCBs and PBDEs, halogenated BPA and genistein. These results show that the hydroxylated metabolites of the ubiquitous PBDEs not only target the T4 transport at the TTR level, but also, and to a great extent, at the TBG level where most of the T4 in humans is circulating. The optimized SPR biosensor-based transport protein assay is a suitable method for high throughput screening of large libraries for potential thyroid hormone disrupting compounds

  9. Biosensor discovery of thyroxine transport disrupting chemicals.

    Science.gov (United States)

    Marchesini, Gerardo R; Meimaridou, Anastasia; Haasnoot, Willem; Meulenberg, Eline; Albertus, Faywell; Mizuguchi, Mineyuki; Takeuchi, Makoto; Irth, Hubertus; Murk, Albertinka J

    2008-10-01

    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 inhibition assays using the main thyroid hormone transport proteins, T4 binding globulin (TBG) and transthyretin (TTR), in combination with a T4-coated biosensor chip were optimized and automated for screening chemical libraries. The transport protein-based biosensor assays were rapid, high throughput and bioeffect-related. A library of 62 chemicals including the natural hormones, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and metabolites, halogenated bisphenol A (BPA), halogenated phenols, pharmaceuticals, pesticides and other potential environmentally relevant chemicals was tested with the two assays. We discovered ten new active compounds with moderate to high affinity for TBG with the TBG assay. Strikingly, the most potent binding was observed with hydroxylated metabolites of the brominated diphenyl ethers (BDEs) BDE 47, BDE 49 and BDE 99, that are commonly found in human plasma. The TTR assay confirmed the activity of previously identified hydroxylated metabolites of PCBs and PBDEs, halogenated BPA and genistein. These results show that the hydroxylated metabolites of the ubiquitous PBDEs not only target the T4 transport at the TTR level, but also, and to a great extent, at the TBG level where most of the T4 in humans is circulating. The optimized SPR biosensor-based transport protein assay is a suitable method for high throughput screening of large libraries for potential thyroid hormone disrupting compounds.

  10. Thyroid effects of endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

    2012-01-01

    In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert ...... thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties....

  11. Sideways Force Produced During Disruptions

    Science.gov (United States)

    Strauss, H. R.; Paccagnella, R.; Breslau, J.; Jardin, S.; Sugiyama, L.

    2012-10-01

    We extend previous studies [1] of vertical displacement events (VDE) which can produce disruptions. The emphasis is on the non axisymmetric ``sideways'' wall force Fx. Simulations are performed using the M3D [2] code. A VDE expels magnetic flux through the resistive wall until the last closed flux surface has q VDE is presented. The wall force depends strongly on γτw, where γ is the mode growth rate and τw is the wall resistive penetration time. The force Fx is largest when γτw is a constant of order unity, which depends on the initial conditions. For large values of γτw, the wall force asymptotes to a relatively smaller value, well below the critical value ITER is designed to withstand. The principle of disruption mitigation by massive gas injection is to cause a disruption with large γτw. [4pt] [1] H. R. Strauss, R. Paccagnella, and J. Breslau,Phys. Plasmas 17, 082505 (2010) [2] W. Park, E.V. Belova, G.Y. Fu, X. Tang, H.R. Strauss, L.E. Sugiyama, Phys. Plasmas 6, 1796 (1999).

  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. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

    OpenAIRE

    Ciss?, Yasmine M.; Russart, Kathryn L.G.; Nelson, Randy J.

    2017-01-01

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to eit...

  15. Probabilistic analysis of tokamak plasma disruptions

    International Nuclear Information System (INIS)

    Sanzo, D.L.; Apostolakis, G.E.

    1985-01-01

    An approximate analytical solution to the heat conduction equations used in modeling component melting and vaporization resulting from plasma disruptions is presented. This solution is then used to propagate uncertainties in the input data characterizing disruptions, namely, energy density and disruption time, to obtain a probabilistic description of the output variables of interest, material melted and vaporized. (orig.)

  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. 3rd Annual Disruptive Technology Conference

    Science.gov (United States)

    2006-09-07

    Panel -- The Warfighter’s Perspective The Impact of Disruptive Technologies on Joint Warfighting MG Michael Vane, USA, Vice Director for Force...Structure, Resources & Assessment, Joint Staff, J-8 Panel -- Perspectives of Change: Identifying the Emerging Commercial Disruptive Technologies Decision...Mark Lucas, Board Member OSGeo, RadiantBlue Technologies Panel -- The Search for Disruptive Technologies - a “Blue Force” Multiplier Advanced

  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. Statistical analysis of disruptions in JET

    International Nuclear Information System (INIS)

    De Vries, P.C.; Johnson, M.F.; Segui, I.

    2009-01-01

    The disruption rate (the percentage of discharges that disrupt) in JET was found to drop steadily over the years. Recent campaigns (2005-2007) show a yearly averaged disruption rate of only 6% while from 1991 to 1995 this was often higher than 20%. Besides the disruption rate, the so-called disruptivity, or the likelihood of a disruption depending on the plasma parameters, has been determined. The disruptivity of plasmas was found to be significantly higher close to the three main operational boundaries for tokamaks; the low-q, high density and β-limit. The frequency at which JET operated close to the density-limit increased six fold over the last decade; however, only a small reduction in disruptivity was found. Similarly the disruptivity close to the low-q and β-limit was found to be unchanged. The most significant reduction in disruptivity was found far from the operational boundaries, leading to the conclusion that the improved disruption rate is due to a better technical capability of operating JET, instead of safer operations close to the physics limits. The statistics showed that a simple protection system was able to mitigate the forces of a large fraction of disruptions, although it has proved to be at present more difficult to ameliorate the heat flux.

  20. 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…

  1. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  2. Disruption-induced poloidal currents in the tokamak wall

    International Nuclear Information System (INIS)

    Pustovitov, V.D.

    2017-01-01

    Highlights: • Induction effects during disruptions and rapid transient events in tokamaks. • Plasma-wall electromagnetic interaction. • Flux-conserving evolution of plasma equilibrium. • Poloidal current induced in the vacuum vessel wall in a tokamak. • Complete analytical derivations and estimates. - Abstract: The poloidal current induced in the tokamak wall during fast transient events is analytically evaluated. The analysis is based on the electromagnetic relations coupled with plasma equilibrium equations. The derived formulas describe the consequences of both thermal and current quenches. In the final form, they give explicit dependence of the wall current on the plasma pressure and current. A comparison with numerical results of Villone et al. [F. Villone, G. Ramogida, G. Rubinacci, Fusion Eng. Des. 93, 57 (2015)] for IGNITOR is performed. Our analysis confirms the importance of the effects described there. The estimates show that the disruption-induced poloidal currents in the wall should be necessarily taken into account in the studies of disruptions and disruption mitigation in ITER.

  3. Beryllium and graphite performance in ITER during a disruption

    International Nuclear Information System (INIS)

    Hassanein, A.; Ehst, D.A.; Gahl, J.

    1993-09-01

    Plasma disruptions are considered one of the most limiting factors for successful operation of magnetic fusion reactors. During a disruption, a sharp, rapid release of energy strikes components such as the divertor or limiter plates. Severe surface erosion and melting of these components may then occur. The amount of material eroded from both ablation and melting is important to the reactor design and component lifetime. The anticipated performance of both beryllium and graphite as plasma-facing materials during such abnormal events is analyzed and compared. Recent experimental data obtained with both plasma guns and electron beams are carefully evaluated and compared to results of analytical modeling, including vapor shielding effect. Initial results from plasma gun experiments indicate that the Be erosion rate is about five times larger than that for a graphite material under the same disruption conditions. Key differences between simulation experiments and reactor disruption on the net erosion rate, and consequently on the lifetime of the divertor plate, are discussed in detail. The advantages and disadvantages of Be over graphite as a divertor plasma-facing material are discussed

  4. Hydrogeologic effects of natural disruptive events on nuclear waste repositories

    International Nuclear Information System (INIS)

    Davis, S.N.

    1980-06-01

    Some possible hydrogeologic effects of disruptive events that may affect repositories for nuclear waste are described. A very large number of combinations of natural events can be imagined, but only those events which are judged to be most probable are covered. Waste-induced effects are not considered. The disruptive events discussed above are placed into four geologic settings. Although the geology is not specific to given repository sites that have been considered by other agencies, the geology has been generalized from actual field data and is, therefore, considered to be physically reasonable. The geologic settings considered are: (1) interior salt domes of the Gulf Coast, (2) bedded salt of southeastern New Mexico, (3) argillaceous rocks of southern Nevanda, and (4) granitic stocks of the Basin and Range Province. Log-normal distributions of permeabilities of rock units are given for each region. Chapters are devoted to: poresity and permeability of natural materials, regional flow patterns, disruptive events (faulting, dissolution of rock forming minerals, fracturing from various causes, rapid changes of hydraulic regimen); possible hydrologic effects of disruptive events; and hydraulic fracturing

  5. Disruption of River Networks in Nature and Models

    Science.gov (United States)

    Perron, J. T.; Black, B. A.; Stokes, M.; McCoy, S. W.; Goldberg, S. L.

    2017-12-01

    Many natural systems display especially informative behavior as they respond to perturbations. Landscapes are no exception. For example, longitudinal elevation profiles of rivers responding to changes in uplift rate can reveal differences among erosional mechanisms that are obscured while the profiles are in equilibrium. The responses of erosional river networks to perturbations, including disruption of their network structure by diversion, truncation, resurfacing, or river capture, may be equally revealing. In this presentation, we draw attention to features of disrupted erosional river networks that a general model of landscape evolution should be able to reproduce, including the consequences of different styles of planetary tectonics and the response to heterogeneous bedrock structure and deformation. A comparison of global drainage directions with long-wavelength topography on Earth, Mars, and Saturn's moon Titan reveals the extent to which persistent and relatively rapid crustal deformation has disrupted river networks on Earth. Motivated by this example and others, we ask whether current models of river network evolution adequately capture the disruption of river networks by tectonic, lithologic, or climatic perturbations. In some cases the answer appears to be no, and we suggest some processes that models may be missing.

  6. Beryllium and graphite performance in ITER during a disruption

    International Nuclear Information System (INIS)

    Hassanein, A.; Ehst, D.A.; Gahl, J.

    1994-01-01

    Plasma disruptions are considered one of the most limiting factors for successful operation of magnetic fusion reactors. During a disruption, a sharp, rapid release of energy strikes components such as the divertor or limiter plates. Severe surface erosion and melting of these components may then occur. The amount of material eroded from both ablation and melting is important to the reactor design and component lifetime. The anticipated performance of both beryllium and graphite as plasma-facing materials during such abnormal events is analyzed and compared. Recent experimental data obtained with both plasma guns and electron beams are carefully evaluated and compared to results of analytical modeling, including vapor shielding effect. Initial results from plasma gun experiments indicate that the Be erosion rate is about five times larger than that for a graphite material under the same disruption conditions. Key differences between simulation experiments and reactor disruption on the net erosion rate, and consequently on the lifetime of the divertor plate, are discussed in detail. The advantages and disadvantages of Be over graphite as a divertor plasma-facing material are discussed. ((orig.))

  7. Disruption-induced poloidal currents in the tokamak wall

    Energy Technology Data Exchange (ETDEWEB)

    Pustovitov, V.D., E-mail: Pustovitov_VD@nrcki.ru [National Research Centre ‘Kurchatov Institute’, Pl. Kurchatova 1, Moscow 123182 (Russian Federation); National Research Nuclear University MEPhI, Kashirskoe sh. 31, Moscow 115409, Russia (Russian Federation)

    2017-04-15

    Highlights: • Induction effects during disruptions and rapid transient events in tokamaks. • Plasma-wall electromagnetic interaction. • Flux-conserving evolution of plasma equilibrium. • Poloidal current induced in the vacuum vessel wall in a tokamak. • Complete analytical derivations and estimates. - Abstract: The poloidal current induced in the tokamak wall during fast transient events is analytically evaluated. The analysis is based on the electromagnetic relations coupled with plasma equilibrium equations. The derived formulas describe the consequences of both thermal and current quenches. In the final form, they give explicit dependence of the wall current on the plasma pressure and current. A comparison with numerical results of Villone et al. [F. Villone, G. Ramogida, G. Rubinacci, Fusion Eng. Des. 93, 57 (2015)] for IGNITOR is performed. Our analysis confirms the importance of the effects described there. The estimates show that the disruption-induced poloidal currents in the wall should be necessarily taken into account in the studies of disruptions and disruption mitigation in ITER.

  8. New Players in Immunity to Tuberculosis: The Host Microbiome, Lung Epithelium, and Innate Immune Cells

    Science.gov (United States)

    Gupta, Nancy; Kumar, Rakesh; Agrawal, Babita

    2018-01-01

    Tuberculosis (TB) is a highly contagious infection and devastating chronic disease, causing 10.4 million new infections and 1.8 million deaths every year globally. Efforts to control and eradicate TB are hampered by the rapid emergence of drug resistance and limited efficacy of the only available vaccine, BCG. Immunological events in the airways and lungs are of major importance in determining whether exposure to Mycobacterium tuberculosis (Mtb) results in successful infection or protective immunity. Several studies have demonstrated that the host microbiota is in constant contact with the immune system, and thus continually directs the nature of immune responses occurring during new infections. However, little is known about its role in the eventual outcome of the mycobacterial infection. In this review, we highlight the changes in microbial composition in the respiratory tract and gut that have been linked to the alteration of immune responses, and to the risk, prevention, and treatment of TB. In addition, we summarize our current understanding of alveolar epithelial cells and the innate immune system, and their interaction with Mtb during early infection. Extensive studies are warranted to fully understand the all-inclusive role of the lung microbiota, its interaction with epithelium and innate immune responses and resulting adaptive immune responses, and in the pathogenesis and/or protection from Mtb infection. Novel interventions aimed at influencing the microbiota, the alveolar immune system and innate immunity will shape future strategies of prevention and treatment for TB. PMID:29692778

  9. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. From Digital Disruption to Business Model Scalability

    DEFF Research Database (Denmark)

    Nielsen, Christian; Lund, Morten; Thomsen, Peter Poulsen

    2017-01-01

    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...... will seldom lead to business model scalability capable of competing with digital disruption(s)....... 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...

  11. Immunity to poliovirus after infection and vaccination

    NARCIS (Netherlands)

    Herremans, Martina Maria Petronella Theresia

    1999-01-01

    The aim of this thesis was defined as the study of the contribution of IPV vaccination to the induction of a) protection against poliovirus infection and b) mucosal immunity.We have described the development of new immunological tools for the rapid detection of poliovirus-specific antibodies and

  12. Immune System (For Parents)

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario The immune system, which is made up ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  13. Immunity by equilibrium.

    Science.gov (United States)

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  14. Immunity's ancient arms

    OpenAIRE

    Litman, Gary W.; Cannon, John P.

    2009-01-01

    Diverse receptors on two types of cell mediate adaptive immunity in jawed vertebrates. In the lamprey, a jawless vertebrate, immunity is likewise compartmentalized but the molecular mechanics are very different.

  15. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  16. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  17. Aging changes in immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. AGING CHANGES AND THEIR EFFECTS ON THE IMMUNE SYSTEM ...

  18. Immunizations for adult women.

    Science.gov (United States)

    Faubion, Stephanie S; Larkin, Lisa C

    2016-12-01

    Immunizations protect individual persons and contribute to public health by reducing morbidity and mortality associated with common infectious diseases. In this Practice Pearl, we review guidelines for adult immunizations and recent and potential changes in vaccines.

  19. Frosted branch angiitis associated with rapidly progressive glomerulonephritis.

    Directory of Open Access Journals (Sweden)

    Gupta Amod

    2002-01-01

    Full Text Available Simultaneous occurrence of frosted branch angiitis and immune-mediated rapidly progressive glomerulonephritis is reported. The two diseases possibly share a common immune mechanism. Patients of frosted branch angiitis should undergo complete systemic evaluation including renal function tests even if the patient is systemically asymptomatic.

  20. Towards a Disruptive Digital Platform Model

    DEFF Research Database (Denmark)

    Kazan, Erol

    that digital platforms leverage on three strategic design elements (i.e., business, architecture, and technology design) to create supportive conditions for facilitating disruption. To shed light on disruptive digital platforms, I opted for payment platforms as my empirical context and unit of analysis......Digital platforms are layered modular information technology architectures that support disruption. Digital platforms are particularly disruptive, as they facilitate the quick release of digital innovations that may replace established innovations. Yet, despite their support for disruption, we have...... not fully understood how such digital platforms can be strategically designed and configured to facilitate disruption. To that end, this thesis endeavors to unravel disruptive digital platforms from the supply perspective that are grounded on strategic digital platform design elements. I suggest...

  1. The role of intestinal microbiota and the immune system.

    Science.gov (United States)

    Purchiaroni, F; Tortora, A; Gabrielli, M; Bertucci, F; Gigante, G; Ianiro, G; Ojetti, V; Scarpellini, E; Gasbarrini, A

    2013-02-01

    The human gut is an ecosystem consisting of a great number of commensal bacteria living in symbiosis with the host. Several data confirm that gut microbiota is engaged in a dynamic interaction with the intestinal innate and adaptive immune system, affecting different aspects of its development and function. To review the immunological functions of gut microbiota and improve knowledge of its therapeutic implications for several intestinal and extra-intestinal diseases associated to dysregulation of the immune system. Significant articles were identified by literature search and selected based on content, including atopic diseases, inflammatory bowel diseases and treatment of these conditions with probiotics. Accumulating evidence indicates that intestinal microflora has protective, metabolic, trophic and immunological functions and is able to establish a "cross-talk" with the immune component of mucosal immunity, comprising cellular and soluble elements. When one or more steps in this fine interaction fail, autoimmune or auto-inflammatory diseases may occur. Furthermore, it results from the data that probiotics, used for the treatment of the diseases caused by the dysregulation of the immune system, can have a beneficial effect by different mechanisms. Gut microbiota interacts with both innate and adaptive immune system, playing a pivotal role in maintenance and disruption of gut immune quiescence. A cross talk between the mucosal immune system and endogenous microflora favours a mutual growth, survival and inflammatory control of the intestinal ecosystem. Based on these evidences, probiotics can be used as an ecological therapy in the treatment of immune diseases.  

  2. Innate immune response development in nestling tree swallows

    Science.gov (United States)

    Stambaugh, T.; Houdek, B.J.; Lombardo, M.P.; Thorpe, P.A.; Caldwell, Hahn D.

    2011-01-01

    We tracked the development of innate immunity in nestling Tree Swallows (Tachycineta bicolor) and compared it to that of adults using blood drawn from nestlings during days 6, 12, and 18 of the ???20-day nestling period and from adults. Innate immunity was characterized using an in vitro assay of the ability of whole blood to kill Escherichia coli. The ability of whole blood to kill E. coli increased as nestlings matured. Neither this component of innate immunity nor right wing chord length on day18 were as developed as in adults indicating that development of the innate immune system and growth both continued after fledging. Narrow sense heritability analyses suggest that females with strong immune responses produced nestlings with strong immune responses. These data suggest nestling Tree Swallows allocated sufficient energy to support rapid growth to enable fledging by day 18, but that further development of innate immunity occurred post-fledging. ?? 2011 by the Wilson Ornithological Society.

  3. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

  4. The Immune System Game

    Science.gov (United States)

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  5. Plant innate immunity

    Indian Academy of Sciences (India)

    Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and ...

  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...... recent revision to the Tobacco Products Directive. Medical and public health professionals that control tobacco issues were challenged by a coalition of e-cigarette industry representatives, e-cigarette users, and liberal politicians. The challengers drew on the contending norm of harm reduction...

  7. 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.

  8. Physical and metallurgical phenomena during simulations of plasma disruptions

    International Nuclear Information System (INIS)

    Brossa, F.; Cambini, M.; Quataert, D.; Rigon, G.; Schiller, P.

    1988-01-01

    The metallographic analysis executed on austenitic stainless steel specimens subjected to simulated plasma disruptions allows us to present a complete picture of the most important phenomena. (i) The experiments show that for the calculation of melt layer and evaporation it is necessary to take considerable convection in the melt layer into account. (ii) The rapid solidification of the melt layer leads to a change in the crystalline structure and to the formation of cracks. (iii) Alloying elements with a high vapour pressure evaporate preferentially. (iv) The stresses generated during cooling induce in some case phase changes. (v) During neutron irradiation helium is formed in all first wall materials by (n, α) processes. This helium forms bubbles under disruptions. (orig.)

  9. Modulation of Immune Functions by Foods

    Directory of Open Access Journals (Sweden)

    Shuichi Kaminogawa

    2004-01-01

    Full Text Available Evidence is rapidly accumulating as to the beneficial effects of foods. However, it is not always clear whether the information is based on data evaluated impartially in a scientific fashion. Human research into whether foods modulate immune functions in either intervention studies or randomized controlled trials can be classified into three categories according to the physical state of subjects enrolled for investigation: (i studies examining the effect of foods in healthy individuals; (ii studies analyzing the effect of foods on patients with hypersensitivity; and (iii studies checking the effect of foods on immunocompromized subjects, including patients who had undergone surgical resection of cancer and newborns. The systematization of reported studies has made it reasonable to conclude that foods are able to modulate immune functions manifesting as either innate immunity (phagocytic activity, NK cell activity or acquired immunity (T cell response, antibody production. Moreover, improvement of immune functions by foods can normalize the physical state of allergic patients or cancer patients, and may reduce the risk of diseases in healthy individuals. Therefore, it is valuable to assess the immune-modulating abilities of foods by measuring at least one parameter of either innate or acquired immunity.

  10. Innate and Adaptive Immunity to Mucorales.

    Science.gov (United States)

    Ghuman, Harlene; Voelz, Kerstin

    2017-09-05

    Mucormycosis is an invasive fungal infection characterised by rapid filamentous growth, which leads to angioinvasion, thrombosis, and tissue necrosis. The high mortality rates (50-100%) associated with mucormycosis are reflective of not only the aggressive nature of the infection and the poor therapeutics currently employed, but also the failure of the human immune system to successfully clear the infection. Immune effector interaction with Mucorales is influenced by the developmental stage of the mucormycete spore. In a healthy immune environment, resting spores are resistant to phagocytic killing. Contrarily, swollen spores and hyphae are susceptible to damage and degradation by macrophages and neutrophils. Under the effects of immune suppression, the recruitment and efficacy of macrophage and neutrophil activity against mucormycetes is considerably reduced. Following penetration of the endothelial lining, Mucorales encounter platelets. Platelets adhere to both mucormycete spores and hyphae, and exhibit germination suppression and hyphal damage capacity in vitro. Dendritic cells are activated in response to Mucorales hyphae only, and induce adaptive immunity. It is crucial to further knowledge regarding our immune system's failure to eradicate resting spores under intact immunity and inhibit fungal growth under immunocompromised conditions, in order to understand mucormycosis pathogenicity and enhance therapeutic strategies for mucormycosis.

  11. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  12. Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms.

    Science.gov (United States)

    Kang, Sangmin; Myoung, Jinjong

    2017-10-28

    Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.

  13. Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits.

    Science.gov (United States)

    Mossman, K; Lee, S F; Barry, M; Boshkov, L; McFadden, G

    1996-07-01

    Myxoma virus is a pathogenic poxvirus that induces a lethal myxomatosis disease profile in European rabbits, which is characterized by fulminating lesions at the primary site of inoculation, rapid dissemination to secondary internal organs and peripheral external sites, and supervening gram-negative bacterial infection. Here we describe the role of a novel myxoma virus protein encoded by the M-T5 open reading frame during pathogenesis. The myxoma virus M-T5 protein possesses no significant sequence homology to nonviral proteins but is a member of a larger poxviral superfamily designated host range proteins. An M-T5- mutant virus was constructed by disruption of both copies of the M-T5 gene followed by insertion of the selectable marker p7.5Ecogpt. Although the M-T5- deletion mutant replicated with wild-type kinetics in rabbit fibroblasts, infection of a rabbit CD4+ T-cell line (RL5) with the myxoma virus M-T5- mutant virus resulted in the rapid and complete cessation of both host and viral protein synthesis, accompanied by the manifestation of all the classical features of programmed cell death. Infection of primary rabbit peripheral mononuclear cells with the myxoma virus M-T5-mutant virus resulted in the apoptotic death of nonadherent lymphocytes but not adherent monocytes. Within the European rabbit, disruption of the M-T5 open reading frame caused a dramatic attenuation of the rapidly lethal myxomatosis infection, and none of the infected rabbits displayed any of the characteristic features of myxomatosis. The two most significant histological observations in rabbits infected with the M-T5-mutant virus were (i) the lack of progression of the infection past the primary site of inoculation, coupled with the establishment of a rapid and effective inflammatory reaction, and (ii) the inability of the virus to initiate a cellular reaction within secondary immune organs. We conclude that M-T5 functions as a critical virulence factor by allowing productive infection of

  14. 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.

  15. Modeling SOL evolution during disruptions

    International Nuclear Information System (INIS)

    Rognlien, T.D.; Cohen, R.H.; Crotinger, J.A.

    1996-01-01

    We present the status of our models and transport simulations of the 2-D evolution of the scrape-off layer (SOL) during tokamak disruptions. This evolution is important for several reasons: It determines how the power from the core plasma is distributed on material surfaces, how impurities from those surfaces or from gas injection migrate back to the core region, and what are the properties of the SOL for carrying halo currents. We simulate this plasma in a time-dependent fashion using the SOL transport code UEDGE. This code models the SOL plasma using fluid equations of plasma density, parallel momentum (along the magnetic field), electron energy, ion energy, and neutral gas density. A multispecies model is used to follow the density of different charge-states of impurities. The parallel transport is classical but with kinetic modifications; these are presently treated by flux limits, but we have initiated more sophisticated models giving the correct long-mean-free path limit. The cross-field transport is anomalous, and one of the results of this work is to determine reasonable values to characterize disruptions. Our primary focus is on the initial thermal quench phase when most of the core energy is lost, but the total current is maintained. The impact of edge currents on the MHD equilibrium will be discussed

  16. Monitoring-induced disruption in skilled typewriting.

    Science.gov (United States)

    Snyder, Kristy M; Logan, Gordon D

    2013-10-01

    It is often disruptive to attend to the details of one's expert performance. The current work presents four experiments that utilized a monitor to report protocol to evaluate the sufficiency of three accounts of monitoring-induced disruption. The inhibition hypothesis states that disruption results from costs associated with preparing to withhold inappropriate responses. The dual-task hypothesis states that disruption results from maintaining monitored information in working memory. The implicit-explicit hypothesis states that disruption results from explicitly monitoring details of performance that are normally implicit. The findings suggest that all three hypotheses are sufficient to produce disruption, but inhibition and dual-task costs are not necessary. Experiment 1 showed that monitoring to report was disruptive even when there was no requirement to inhibit. Experiment 2 showed that maintaining information in working memory caused some disruption but much less than monitoring to report. Experiment 4 showed that monitoring to inhibit was more disruptive than monitoring to report, suggesting that monitoring is more disruptive when it is combined with other task requirements, such as inhibition. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  17. Rapid flow imaging method

    International Nuclear Information System (INIS)

    Pelc, N.J.; Spritzer, C.E.; Lee, J.N.

    1988-01-01

    A rapid, phase-contrast, MR imaging method of imaging flow has been implemented. The method, called VIGRE (velocity imaging with gradient recalled echoes), consists of two interleaved, narrow flip angle, gradient-recalled acquisitions. One is flow compensated while the second has a specified flow encoding (both peak velocity and direction) that causes signals to contain additional phase in proportion to velocity in the specified direction. Complex image data from the first acquisition are used as a phase reference for the second, yielding immunity from phase accumulation due to causes other than motion. Images with pixel values equal to MΔΘ where M is the magnitude of the flow compensated image and ΔΘ is the phase difference at the pixel, are produced. The magnitude weighting provides additional vessel contrast, suppresses background noise, maintains the flow direction information, and still allows quantitative data to be retrieved. The method has been validated with phantoms and is undergoing initial clinical evaluation. Early results are extremely encouraging

  18. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  19. Kidney and innate immunity.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  20. Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    Luis Fernando Cadavid Gutierrez

    2011-09-01

    Full Text Available The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests during evolution different animal groups have found alternative solutions to the problem of immune recognition.

  1. As-CATH1-6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses.

    Science.gov (United States)

    Chen, Yan; Cai, Shasha; Qiao, Xue; Wu, Mali; Guo, Zhilai; Wang, Renping; Kuang, Yi-Qun; Yu, Haining; Wang, Yipeng

    2017-08-10

    Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of the crocodilian immune system have remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1-6) were identified and characterized from the endangered Chinese alligator ( Alligator sinensis ). As-CATH1-6 exhibit no sequence similarity with any of the known cathelicidins. Structure analysis indicated that As-CATH1-3 adopt a random coil secondary conformation, whereas As-CATH4-6 were predicted to mainly adopt an amphipathic α-helix conformation. Among them, As-CATH4-6 exhibited potent, broad-spectrum and rapid antimicrobial activity by inducing the disruption of cell membrane integrity. They also exhibited strong ability to prevent the formation of bacterial biofilms and eradicate preformed biofilms. Furthermore, As-CATH4-6 exhibited potent anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and pro-inflammatory cytokines in mouse peritoneal macrophages. They directly neutralized LPS toxicity and therefore inhibited the binding of LPS to the TLR4 receptor and the subsequent activation of inflammatory response pathways. In a peritonitis mice model, As-CATH2-6 provided effective protection against bacterial infection through enhanced immune cell recruitment. In the host Chinese alligator, As-CATH1-6 are mainly expressed in immune organs and epithelial tissues. Bacterial infection significantly enhances their expression, which implies an important role in host anti-infective response. Taken together, the diversity and multiple functions of As-CATH1-6 partially reveal the powerful immune system of the Chinese alligator. © 2017 The Author(s). Published by Portland

  2. Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

    Science.gov (United States)

    Marcu, Oana; Lera, Matthew P.; Sanchez, Max E.; Levic, Edina; Higgins, Laura A.; Shmygelska, Alena; Fahlen, Thomas F.; Nichol, Helen; Bhattacharya, Sharmila

    2011-01-01

    Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways. PMID:21264297

  3. Innate immune responses of Drosophila melanogaster are altered by spaceflight.

    Directory of Open Access Journals (Sweden)

    Oana Marcu

    2011-01-01

    Full Text Available Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways.

  4. Designing Endocrine Disruption Out of the Next Generation of Chemicals.

    Science.gov (United States)

    Schug, T T; Abagyan, R; Blumberg, B; Collins, T J; Crews, D; DeFur, P L; Dickerson, S M; Edwards, T M; Gore, A C; Guillette, L J; Hayes, T; Heindel, J J; Moores, A; Patisaul, H B; Tal, T L; Thayer, K A; Vandenberg, L N; Warner, J; Watson, C S; Saal, F S Vom; Zoeller, R T; O'Brien, K P; Myers, J P

    2013-01-01

    A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at "the drawing board." It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a 'proof-of-principle' test, we ran 6 endocrine disrupting chemicals (EDCs) that act via

  5. The Epitranscriptome and Innate Immunity.

    Directory of Open Access Journals (Sweden)

    Mary A O'Connell

    2015-12-01

    Full Text Available Our knowledge of the variety and abundances of RNA base modifications is rapidly increasing. Modified bases have critical roles in tRNAs, rRNAs, translation, splicing, RNA interference, and other RNA processes, and are now increasingly detected in all types of transcripts. Can new biological principles associated with this diversity of RNA modifications, particularly in mRNAs and long non-coding RNAs, be identified? This review will explore this question by focusing primarily on adenosine to inosine (A-to-I RNA editing by the adenine deaminase acting on RNA (ADAR enzymes that have been intensively studied for the past 20 years and have a wide range of effects. Over 100 million adenosine to inosine editing sites have been identified in the human transcriptome, mostly in embedded Alu sequences that form potentially innate immune-stimulating dsRNA hairpins in transcripts. Recent research has demonstrated that inosine in the epitranscriptome and ADAR1 protein establish innate immune tolerance for host dsRNA formed by endogenous sequences. Innate immune sensors that detect viral nucleic acids are among the readers of epitranscriptome RNA modifications, though this does preclude a wide range of other modification effects.

  6. Measuring polio immunity to plan immunization activities.

    Science.gov (United States)

    Voorman, Arend; Lyons, Hil M

    2016-11-21

    The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. β limit disruptions in the TFTR tokamak

    International Nuclear Information System (INIS)

    Fredrickson, E.D.; McGuire, K.; Janos, A.; Bell, M.; Budny, R.V.; Bush, C.E.; Manickam, J.; Mynick, H.; Nazikian, R.; Taylor, G.

    1994-11-01

    A disruptive β limit (β = plasma pressure/magnetic pressure) is observed in high performance plasmas in TFTR. The MHD character of these disruptions differs substantially from the disruptions in high density plasmas (density limit disruptions) on TFTR. The high β disruptions can occur with less than a milliseconds warning in the form of a fast growing precursor. The precursor appears to be an external kink or internal (m,n)=(1,1) kink strongly coupled through finite β effects and toroidal terms to higher m components. It does not have the open-quote cold bubble close-quote structure found in density limit disruptions. There is also no evidence for a change in the internal inductance, i.e., a major reconnection of the flux, at the time of the thermal quench

  8. The Effects of Disruption on Strategic Management

    DEFF Research Database (Denmark)

    Drejer, Anders

    2017-01-01

    There is a lot of interest in Disruption these days even though the concept itself is still under formation. Disruption can be traced back to the idea of disruptive technological change and the late 1990s but has reemerged in the public eye in current years under guises such as Big Data......, 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....

  9. 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

    2018-05-01

    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 noninflammatory 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. Because 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. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.

  10. Ngoma Herbal Tonic Immune Booster interferes with a rapid uri

    African Journals Online (AJOL)

    the official list of WADA are cannabis, cocaine and ephedra, and they are listed as ... added into the urine sample after collection to alter the results, mainly to cause a .... collected and stored in the refrigerator at 4°C until needed. Six aliquots of ...

  11. Multistage Logistic Network Optimization under Disruption Risk

    OpenAIRE

    Rusman, Muhammad

    2013-01-01

    Getting over disruptions risk has been a challenging issue for many companies under the globalization that will link to potential external source such as demand uncertainties, natural disasters, and terrorist attacks. The disruption is an unexpected event that disturbs normal flows of products and materials within a supply chain. The disruption at one members of supply chain will propagate the offers and finally affect significant impacts on the entire chain. If we look back...

  12. 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)

  13. Incumbent response to disruptive innovation

    DEFF Research Database (Denmark)

    Kaulio, Matti; Thorén, Kent; Rohrbeck, René

    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......This article presents a preliminary analysis of a retrospective longitudinal case study of an incumbent, the Swedish-Finnish Telecom operator TeliaSonera AB, with focus on its responses to technical and business model change. Findings nuance the general understanding of Telco’s as passive actors...... 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...

  14. 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).

  15. 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).

  16. Disruptive colouration and perceptual grouping.

    Science.gov (United States)

    Espinosa, Irene; Cuthill, Innes C

    2014-01-01

    Camouflage is the primary defence of many animals and includes multiple strategies that interfere with figure-ground segmentation and object recognition. While matching background colours and textures is widespread and conceptually straightforward, less well explored are the optical 'tricks', collectively called disruptive colouration, that exploit perceptual grouping mechanisms. Adjacent high contrast colours create false edges, but this is not sufficient for an object's shape to be broken up; some colours must blend with the background. We test the novel hypothesis that this will be particularly effective when the colour patches on the animal appear to belong to, not merely different background colours, but different background objects. We used computer-based experiments where human participants had to find cryptic targets on artificial backgrounds. Creating what appeared to be bi-coloured foreground objects on bi-coloured backgrounds, we generated colour boundaries that had identical local contrast but either lay within or between (illusory) objects. As predicted, error rates for targets matching what appeared to be different background objects were higher than for targets which had otherwise identical local contrast to the background but appeared to belong to single background objects. This provides evidence for disruptive colouration interfering with higher-level feature integration in addition to previously demonstrated low-level effects involving contour detection. In addition, detection was impeded in treatments where targets were on or in close proximity to multiple background colour or tone boundaries. This is consistent with other studies which show a deleterious influence of visual 'clutter' or background complexity on search.

  17. Disruptive colouration and perceptual grouping.

    Directory of Open Access Journals (Sweden)

    Irene Espinosa

    Full Text Available Camouflage is the primary defence of many animals and includes multiple strategies that interfere with figure-ground segmentation and object recognition. While matching background colours and textures is widespread and conceptually straightforward, less well explored are the optical 'tricks', collectively called disruptive colouration, that exploit perceptual grouping mechanisms. Adjacent high contrast colours create false edges, but this is not sufficient for an object's shape to be broken up; some colours must blend with the background. We test the novel hypothesis that this will be particularly effective when the colour patches on the animal appear to belong to, not merely different background colours, but different background objects. We used computer-based experiments where human participants had to find cryptic targets on artificial backgrounds. Creating what appeared to be bi-coloured foreground objects on bi-coloured backgrounds, we generated colour boundaries that had identical local contrast but either lay within or between (illusory objects. As predicted, error rates for targets matching what appeared to be different background objects were higher than for targets which had otherwise identical local contrast to the background but appeared to belong to single background objects. This provides evidence for disruptive colouration interfering with higher-level feature integration in addition to previously demonstrated low-level effects involving contour detection. In addition, detection was impeded in treatments where targets were on or in close proximity to multiple background colour or tone boundaries. This is consistent with other studies which show a deleterious influence of visual 'clutter' or background complexity on search.

  18. Observation of disruptions in tokamak plasma under the influence of resonant helical magnetic fields

    International Nuclear Information System (INIS)

    Araujo, M.; Vannucci, A.; Caldas, I.

    1996-01-01

    Disruptive instabilities were investigated in the small tokamak TBR-1 during the application of resonant helical magnetic fields created by external helical windings. Indications were found that the main triggering mechanism of the disruptions was the rapid increase of the m=2/n=1 mode which, apparently after reaching a certain amplitude, interacts with other resistive modes: the internal 1/1 mode in the case of minor disruptions. After the coupling, the growth of the associated islands would create a chaotic field line distribution in the region between the corresponding rational magnetic surfaces which caused the gross particle transport and, finally, destroyed the confinement. In addition, investigations on higher Z eff discharges in which a mixture of helium and hydrogen was used resulted in much more unstable plasmas but apparently did not alter basic characteristics of the disruptions

  19. Fuel-disruption experiments under high-ramp-rate heating conditions

    International Nuclear Information System (INIS)

    Wright, S.A.; Worledge, D.H.; Cano, G.L.; Mast, P.K.; Briscoe, F.

    1983-10-01

    This topical report presents the preliminary results and analysis of the High Ramp Rate fuel-disruption experiment series. These experiments were performed in the Annular Core Research Reactor at Sandia National Laboratories to investigate the timing and mode of fuel disruption during the prompt-burst phase of a loss-of-flow accident. High-speed cinematography was used to observe the timing and mode of the fuel disruption in a stack of five fuel pellets. Of the four experiments discussed, one used fresh mixed-oxide fuel, and three used irradiated mixed-oxide fuel. Analysis of the experiments indicates that in all cases, the observed disruption occurred well before fuel-vapor pressure was high enough to cause the disruption. The disruption appeared as a rapid spray-like expansion and occurred near the onset of fuel melting in the irradiated-fuel experiments and near the time of complete fuel melting in the fresh-fuel experiment. This early occurrence of fuel disruption is significant because it can potentially lower the work-energy release resulting from a prompt-burst disassembly accident

  20. From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system.

    Science.gov (United States)

    Dhouib, Ines; Jallouli, Manel; Annabi, Alya; Marzouki, Soumaya; Gharbi, Najoua; Elfazaa, Saloua; Lasram, Mohamed Montassar

    2016-05-01

    The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

  1. Nuclear Power Learning and Deployment Rates; Disruption and Global Benefits Forgone

    OpenAIRE

    Peter A. Lang

    2017-01-01

    This paper presents evidence of the disruption of a transition from fossil fuels to nuclear power, and finds the benefits forgone as a consequence are substantial. Learning rates are presented for nuclear power in seven countries, comprising 58% of all power reactors ever built globally. Learning rates and deployment rates changed in the late-1960s and 1970s from rapidly falling costs and accelerating deployment to rapidly rising costs and stalled deployment. Historical nuclear global capacit...

  2. Evasion of the Immune Response by Trypanosoma cruzi during Acute Infection

    Science.gov (United States)

    Cardoso, Mariana S.; Reis-Cunha, João Luís; Bartholomeu, Daniella C.

    2016-01-01

    Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical disease that affects millions of people mainly in Latin America. To establish a life-long infection, T. cruzi must subvert the vertebrate host’s immune system, using strategies that can be traced to the parasite’s life cycle. Once inside the vertebrate host, metacyclic trypomastigotes rapidly invade a wide variety of nucleated host cells in a membrane-bound compartment known as the parasitophorous vacuole, which fuses to lysosomes, originating the phagolysosome. In this compartment, the parasite relies on a complex network of antioxidant enzymes to shield itself from lysosomal oxygen and nitrogen reactive species. Lysosomal acidification of the parasitophorous vacuole is an important factor that allows trypomastigote escape from the extremely oxidative environment of the phagolysosome to the cytoplasm, where it differentiates into amastigote forms. In the cytosol of infected macrophages, oxidative stress instead of being detrimental to the parasite, favors amastigote burden, which then differentiates into bloodstream trypomastigotes. Trypomastigotes released in the bloodstream upon the rupture of the host cell membrane express surface molecules, such as calreticulin and GP160 proteins, which disrupt initial and key components of the complement pathway, while others such as glycosylphosphatidylinositol-mucins stimulate immunoregulatory receptors, delaying the progression of a protective immune response. After an immunologically silent entry at the early phase of infection, T. cruzi elicits polyclonal B cell activation, hypergammaglobulinemia, and unspecific anti-T. cruzi antibodies, which are inefficient in controlling the infection. Additionally, the coexpression of several related, but not identical, epitopes derived from trypomastigote surface proteins delays the generation of T. cruzi-specific neutralizing antibodies. Later in the infection, the establishment of an anti-T. cruzi

  3. Characterization of axisymmetric disruption dynamics toward VDE avoidance in tokamaks

    International Nuclear Information System (INIS)

    Nakamura, Y.

    2002-01-01

    Disruption experiments on Alcator C-Mod and ASDEX-Upgrade tokamaks and axisymmetric MHD simulations using the TSC have explicated the underlying mechanisms of Vertical Displacement Events (VDEs) and a diversity of disruption dynamics. First, the neutral point, which is known as an initial vertical plasma position advantageous to VDE avoidance, is shown to be fairly insensitive to plasma shape and current profile parameters, while the VDE rate significantly depends on those parameters. Secondly, it is clarified that a rapid flattening of the plasma current profile frequently seen at the thermal quench drags a single null-diverted, up-down asymmetric plasma vertically toward divertor, whereas the dragging effect is absent in up-down symmetric limiter discharges. As a consequence, the occurrence of downward-going VDEs predominates over the upward-going ones in bottom-diverted discharges, being consistent with experiments in ASDEX-Upgrade. Together with the attractive force that arises from passive shell currents induced by the current quench and vanishes at the neutral point, the dragging effect explains many details of the VDE dynamics over the whole period of disruptive termination. (author)

  4. Characterization of axisymmetric disruption dynamics toward VDE avoidance in tokamaks

    International Nuclear Information System (INIS)

    Nakamura, Y.; Yoshino, R.; Granetz, R.S.; Pautasso, G.; Gruber, O.; Jardin, S.C.

    2003-01-01

    Experiments and axisymmetric MHD simulations on tokamak disruptions have explicated the underlying mechanisms of Vertical Displacement Events (VDEs) and a diversity of disruption dynamics. First, the neutral point, which is known as an advantageous vertical plasma position to avoiding VDEs during the plasma current quench, is shown to be fairly insensitive to plasma shape and current profile parameters. Secondly, a rapid flattening of the plasma current profile frequently seen at thermal quench is newly clarified to play a substantial role in dragging a single null-diverted plasma vertically towards the divertor. As a consequence, the occurrence of downward-going VDEs predominates over the upward-going ones in bottom diverted discharges. This dragging effect is absent in up-down symmetric limiter discharges. These simulation results are consistent with experiments. Together with the attractive force that arises from passive shell currents and essentially vanishes at the neutral point, the dragging effect explains many details of the VDE dynamics over the whole period of the disruptive termination. (author)

  5. The location of splenic NKT cells favours their rapid activation by blood-borne antigen

    Science.gov (United States)

    Barral, Patricia; Sánchez-Niño, María Dolores; van Rooijen, Nico; Cerundolo, Vincenzo; Batista, Facundo D

    2012-01-01

    Natural killer T (NKT) cells play an important role in mounting protective responses to blood-borne infections. However, though the spleen is the largest blood filter in the body, the distribution and dynamics of NKT cells within this organ are not well characterized. Here we show that the majority of NKT cells patrol around the marginal zone (MZ) and red pulp (RP) of the spleen. In response to lipid antigen, these NKT cells become arrested and rapidly produce cytokines, while the small proportion of NKT cells located in the white pulp (WP) exhibit limited activation. Importantly, disruption of the splenic MZ by chemical or genetic approaches results in a severe reduction in NKT cell activation indicating the need of cooperation between both MZ macrophages and dendritic cells for efficient NKT cell responses. Thus, the location of splenic NKT cells in the MZ and RP facilitates their access to blood-borne antigen and enables the rapid initiation of protective immune responses. PMID:22505026

  6. Dim light at night does not disrupt timing or quality of sleep in mice.

    Science.gov (United States)

    Borniger, Jeremy C; Weil, Zachary M; Zhang, Ning; Nelson, Randy J

    2013-10-01

    Artificial nighttime illumination has recently become commonplace throughout the world; however, in common with other animals, humans have not evolved in the ecological context of chronic light at night. With prevailing evidence linking the circadian, endocrine, immune, and metabolic systems, understanding these relationships is important to understanding the etiology and progression of several diseases. To eliminate the covariate of sleep disruption in light at night studies, researchers often use nocturnal animals. However, the assumption that light at night does not affect sleep in nocturnal animals remains unspecified. To test the effects of light at night on sleep, we maintained Swiss-Webster mice in standard light/dark (LD) or dim light at night (DLAN) conditions for 8-10 wks and then measured electroencephalogram (EEG) and electromyogram (EMG) biopotentials via wireless telemetry over the course of two consecutive days to determine differences in sleep timing and homeostasis. Results show no statistical differences in total percent time, number of episodes, maximum or average episode durations in wake, slow-wave sleep (SWS), or rapid eye movement (REM) sleep. No differences were evident in SWS delta power, an index of sleep drive, between groups. Mice kept in DLAN conditions showed a relative increase in REM sleep during the first few hours after the dark/light transition. Both groups displayed normal 24-h circadian rhythms as measured by voluntary running wheel activity. Groups did not differ in body mass, but a marked negative correlation of body mass with percent time spent awake and a positive correlation of body mass with time spent in SWS was evident. Elevated body mass was also associated with shorter maximum wake episode durations, indicating heavier animals had more trouble remaining in the wake vigilance state for extended periods of time. Body mass did not correlate with activity levels, nor did activity levels correlate with time spent in

  7. Lung Homeostasis: Influence of Age, Microbes, and the Immune System.

    Science.gov (United States)

    Lloyd, Clare M; Marsland, Benjamin J

    2017-04-18

    Pulmonary immune homeostasis is maintained by a network of tissue-resident cells that continually monitor the external environment, and in health, instruct tolerance to innocuous inhaled particles while ensuring that efficient and rapid immune responses can be mounted against invading pathogens. Here we review the multiple pathways that underlie effective lung immunity in health, and discuss how these may be affected by external environmental factors and contribute to chronic inflammation during disease. In this context, we examine the current understanding of the impact of the microbiota in immune development and function and in the setting of the threshold for immune responses that maintains the balance between tolerance and chronic inflammation in the lung. We propose that host interactions with microbes are critical for establishing the immune landscape of the lungs. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.

    Science.gov (United States)

    Roybal, Kole T; Lim, Wendell A

    2017-04-26

    The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

  9. Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

    Science.gov (United States)

    Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

    2017-07-20

    Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

  10. Rapid shallow breathing

    Science.gov (United States)

    Tachypnea; Breathing - rapid and shallow; Fast shallow breathing; Respiratory rate - rapid and shallow ... Shallow, rapid breathing has many possible medical causes, including: Asthma Blood clot in an artery in the ...

  11. Ion heating at the disruptive instability in the LT-3 Tokamak

    International Nuclear Information System (INIS)

    Bell, M.G.; Hutchinson, I.H.

    1976-01-01

    Measurements of the ion temperature and the toroidal current density and electric field during the disruptive instability in LT-3 are presented. Rapid ion heating and strong current inhibition have been observed. Fluctuation measurements suggest that these effects may be attributable to the excitation of ion cyclotron drift waves in the plasma

  12. Criteria for initiation of tokamak disruptions

    International Nuclear Information System (INIS)

    Hopcraft, K.I.; Turner, M.F.

    1986-01-01

    The process by which a tokamak plasma evolves from an equilibrium state containing a saturated magnetic island to one which is disruptively unstable is discussed and illustrated by numerical simulation of a resistive magnetoplasma. Those elements which are required to initiate a disruption are delineated

  13. Disruption simulation for the EAST plasma

    International Nuclear Information System (INIS)

    Niu Xingping; Wu Bin

    2007-01-01

    The disruptions due to vertical displacement event for the EAST plasma are simulated in this article by using the TSC program. Meanwhile, the evolutions of the halo current and stress on vacuum vessel are calculated; the disruptions at different initial conditions are compared with each other, and killer pellet injection is simulated for the device fast shutting-down. (authors)

  14. Network Formation under the Threat of Disruption

    NARCIS (Netherlands)

    Hoyer, B.

    2013-01-01

    The studies in this thesis are focused on the impact the presence of a network disruptor has on network formation models. In particular, we build two theoretical models to study the effect of network disruption on network formation and test the effect network disruption has on equilibrium selection

  15. Inventory strategies to manage supply disruptions

    NARCIS (Netherlands)

    Atan, Z.; Snyder, L.V.; Gurnani, H.; Mehrotra, H.; Ray, S.

    2012-01-01

    Disruptions in supply chains occur routinely—both large ones, due to natural disasters, labor strikes, or terrorist attacks, and small ones, due to machine breakdowns, supplier stockouts, or quality problems (to name a few examples). Companies whose supply processes are affected by disruptions may

  16. Simulation of a major tokamak disruption

    International Nuclear Information System (INIS)

    White, R.B.; Monticello, D.A.; Rosenbluth, M.N.

    1977-08-01

    It is known that the internal tokamak disruption leads to a current profile which is flattened inside the surface where the safety factor equals unity. It is shown that such a profile can lead to m = 2 magnetic islands which grow to fill a substantial part of the tokamak cross section in a time consistent with the observations of the major disruption

  17. Disruptive technologies and networking in telecom industries

    DEFF Research Database (Denmark)

    Madsen, Erik Strøjer; Hartington, Simon

    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...

  18. 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

  19. 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

  20. 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 discuss...

  1. 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…

  2. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

    Science.gov (United States)

    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  3. Sideways wall force produced during tokamak disruptions

    Science.gov (United States)

    Strauss, H.; Paccagnella, R.; Breslau, J.; Sugiyama, L.; Jardin, S.

    2013-07-01

    A critical issue for ITER is to evaluate the forces produced on the surrounding conducting structures during plasma disruptions. We calculate the non-axisymmetric ‘sideways’ wall force Fx, produced in disruptions. Simulations were carried out of disruptions produced by destabilization of n = 1 modes by a vertical displacement event (VDE). The force depends strongly on γτwall, where γ is the mode growth rate and τwall is the wall penetration time, and is largest for γτwall = constant, which depends on initial conditions. Simulations of disruptions caused by a model of massive gas injection were also performed. It was found that the wall force increases approximately offset linearly with the displacement from the magnetic axis produced by a VDE. These results are also obtained with an analytical model. Disruptions are accompanied by toroidal variation of the plasma current Iφ. This is caused by toroidal variation of the halo current, as verified computationally and analytically.

  4. 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...... digital platforms purposely decouple platform layers, to foster open innovation and accelerate market disruption. This paper therefore represents a first concrete step aimed at unravelling the disruptive potential of digital platforms....... 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...

  5. Energy flux to the TEXTOR limiters during disruptions

    International Nuclear Information System (INIS)

    Finken, K.H.; Baek, W.Y.; Dippel, K.H.; Boedo, J.A.; Gray, D.S.

    1992-01-01

    Rapidly changing heat fluxes deposited on the limiter blades are observed during disruptions by infrared (IR) scanners. These scanners are a suitable tool for the analysis of these heat fluxes because they provide both spatial and temporal information with sufficient resolution. Several new features of the power flux to the plasma facing surfaces during a disruption have been found. The disruptive heat flux occurs on three different time-scales. The fastest ones are for heat bursts with a duration of ≤0.1 ms; several of these bursts form a thermal quench of about one millisecond duration, and some of these thermal quenches are found to occur during the current decay phase. Power flux densities of the order of 50 MW/m 2 have been observed during a burst. The spatial extent of the area on which this power is deposited during a burst is larger than or equal to the size of half an ALT-II blade, i.e. about 1 m in the toroidal direction. Simultaneous measurements with two cameras show that the correlation length of a single burst is smaller than half the toroidal circumference, probably of the order of half a blade or a full blade length. This is consistent with plasma islands of low mode number. The typical heat deposition patterns at the limiter blades for normal discharges are preserved during a disruption. The magnetic structure near the plasma surface can therefore not be destroyed completely during the thermal quench. The power flux follows the field lines. However, the power e-folding length is about a factor of two to three times larger than under normal discharge conditions. (author). 27 refs, 9 figs

  6. Reinfection immunity in schistosomiasis

    International Nuclear Information System (INIS)

    Kamiya, Haruo

    1987-01-01

    Schistosomiasis is one of the most important parasitic diseases in the world, especially in endemic areas of developing countries. This situation has prompted parasitologist to attempt intensive researches on immune mechanisms, especially those of reinfection immunity associated with eliminating challenge infection. The current knowledge of reinfection immunity against Schistosoma spp. infection was therefore reviewed briefly and discussed with special reference to our data on protective immune responses induced by radiation-attenuated cercarial infection. A recently developed technique of compressed organ autoradiography (COA) has contributed to assessing parasite attrition in immune animals following challenge infection. Our study using COA has demonstrated that major attrition of schistosomula from challenge infection occurs in the skin of CBA/Ca mice vaccinated with 20 Krad gamma radiation-attenuated cercariae of S. mansoni, while in both lungs and liver of similarly vaccinated guinea pig model. Furthermore, gamma-irradiation to cercariae affected their migration potential and surface-antigen profiles. The immunizing stimuli of gamma radiation-attenuated cercariae profoundly affected the expression of responsiveness in vaccinated animals. The change in antigenic profiles and migration potential of those vaccinating population was discussed in relation to the kinetics of reinfection immunity induced in vaccinated amimal models. These works might provide a base line data to develop a practical vaccine for schistosomiasis using defined antigens. It must be emphasized that these vaccines could serve as a practical prophylactic measure for schistosomiasis in the endemic areas, even if the vaccines fail to induce sterilizing immunity. (author). 141 refs

  7. Ethics of Immunization

    NARCIS (Netherlands)

    Verweij, M.F.; Quah, S.R.; Cockerham, W.C.

    2017-01-01

    Collective immunization can be highly effective in protecting societies against infectious diseases, but policy decisions about both the character and the content of immunization policies require ethical justification. This article offers an overview of ethical aspects that should be taken into

  8. Immunity and skin cancer

    International Nuclear Information System (INIS)

    Smith, E.B.; Brysk, M.M.

    1981-01-01

    Observations in humans and animal studies support the theory that immunologic surveillance plays an important role in limiting the development of skin malignancies. These immune responses undergo progressive diminution with age. In addition, other factors, such as bereavement, poor nutrition, and acute and chronic exposure to ultraviolet light, can further diminish immune mechanisms

  9. Immunizations. Position Statement. Revised

    Science.gov (United States)

    Bobo, Nichole; Garrett, Jennifer; Teskey, Carmen; Duncan, Kay; Strasser, Kathy; Burrows-Mezu, Alicia L.

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that immunizations are essential to primary prevention of disease from infancy through adulthood. Promotion of immunizations by the registered professional school nurse (hereinafter referred to as school nurse) is central to the public health focus of school nursing practice…

  10. Disparity in childhood immunizations

    NARCIS (Netherlands)

    Lemstra, Mark; Neudorf, Cory; Opondo, Johnmark; Toye, Jennifer; Kurji, Ayisha; Kunst, Anton; Tournier, Ceal

    2007-01-01

    BACKGROUND: Incomplete immunization coverage is common in low-income families and Aboriginal children in Canada. OBJECTIVE: To determine whether child immunization coverage rates at two years of age were lower in low-income neighbourhoods of Saskatoon, Saskatchewan. METHODS: Parents who were and

  11. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  12. Functional comparison of innate immune signaling pathways in primates.

    Directory of Open Access Journals (Sweden)

    Luis B Barreiro

    2010-12-01

    Full Text Available Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

  13. Recovery of the immune system after exercise.

    Science.gov (United States)

    Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P; Simpson, Richard J

    2017-05-01

    The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8 + T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes. Copyright © 2017 the American Physiological Society.

  14. Microalgal cell disruption via ultrasonic nozzle spraying.

    Science.gov (United States)

    Wang, M; Yuan, W

    2015-01-01

    The objective of this study was to understand the effect of operating parameters, including ultrasound amplitude, spraying pressure, nozzle orifice diameter, and initial cell concentration on microalgal cell disruption and lipid extraction in an ultrasonic nozzle spraying system (UNSS). Two algal species including Scenedesmus dimorphus and Nannochloropsis oculata were evaluated. Experimental results demonstrated that the UNSS was effective in the disruption of microalgal cells indicated by significant changes in cell concentration and Nile red-stained lipid fluorescence density between all treatments and the control. It was found that increasing ultrasound amplitude generally enhanced cell disruption and lipid recovery although excessive input energy was not necessary for best results. The effect of spraying pressure and nozzle orifice diameter on cell disruption and lipid recovery was believed to be dependent on the competition between ultrasound-induced cavitation and spraying-generated shear forces. Optimal cell disruption was not always achieved at the highest spraying pressure or biggest nozzle orifice diameter; instead, they appeared at moderate levels depending on the algal strain and specific settings. Increasing initial algal cell concentration significantly reduced cell disruption efficiency. In all UNSS treatments, the effectiveness of cell disruption and lipid recovery was found to be dependent on the algal species treated.

  15. Dim light at night interferes with the development of the short-day phenotype and impairs cell-mediated immunity in Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    Aubrecht, Taryn G; Weil, Zachary M; Nelson, Randy J

    2014-10-01

    Winter is a challenging time to survive and breed outside of the tropics. Animals use day length (photoperiod) to regulate seasonally appropriate adaptations in anticipation of challenging winter conditions. The net result of these photoperiod-mediated adjustments is enhanced immune function and increased survival. Thus, the ability to discriminate day length information is critical for survival and reproduction in small animals. However, during the past century, urban and suburban development has rapidly expanded and filled the night sky with light from various sources, obscuring crucial light-dark signals, which alters physiological interpretation of day lengths. Furthermore, reduced space, increased proximity to people, and the presence of light at night may act as stressors for small animals. Whereas acute stressors typically enhance immune responses, chronic exposure to stressors often impairs immune responses. Therefore, we hypothesized that the combination of dim light at night and chronic stress interferes with enhanced cell-mediated immunity observed during short days. Siberian hamsters (Phodopus sungorus) were assigned to short or long days with dark nights (0 lux) or dim (5 lux) light at night for 10 weeks. Following 2 weeks of chronic restraint (6 hr/day), a model of chronic stress, delayed type hypersensitivity (DTH) responses were assessed. Both dim light at night and restraint reduced the DTH response. Dim light at night during long nights produced an intermediate short day phenotype. These results suggest the constant presence of light at night could negatively affect survival of photoperiodic rodents by disrupting the timing of breeding and immune responses. © 2014 Wiley Periodicals, Inc.

  16. Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

    Science.gov (United States)

    Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

    2017-01-01

    Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

  17. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular disrupting agent, combretastatin A4 phosphate in mice.

    OpenAIRE

    Welford, Abigail F.; Biziato, Daniela; Coffelt, Seth B.; Nucera, Silvia; Fisher, Matthew; Pucci, Ferdinando; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele; Tozer, Gillian M.; Lewis, Claire E.

    2011-01-01

    Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA...

  18. Rice Snl6, a cinnamoyl-CoA reductase-like gene family member, is required for NH1-mediated immunity to Xanthomonas oryzae pv. oryzae.

    Directory of Open Access Journals (Sweden)

    Rebecca S Bart

    2010-09-01

    Full Text Available Rice NH1 (NPR1 homolog 1 is a key mediator of innate immunity. In both plants and animals, the innate immune response is often accompanied by rapid cell death at the site of pathogen infection. Over-expression of NH1 in rice results in resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo, constitutive expression of defense related genes and enhanced benzothiadiazole (BTH- mediated cell death. Here we describe a forward genetic screen that identified a suppressor of NH1-mediated lesion formation and resistance, snl6. Comparative genome hybridization and fine mapping rapidly identified the genomic location of the Snl6 gene. Snl6 is a member of the cinnamoyl-CoA reductase (CCR-like gene family. We show that Snl6 is required for NH1-mediated resistance to Xoo. Further, we show that Snl6 is required for pathogenesis-related gene expression. In contrast to previously described CCR family members, disruption of Snl6 does not result in an obvious morphologic phenotype. Snl6 mutants have reduced lignin content and increased sugar extractability, an important trait for the production of cellulosic biofuels. These results suggest the existence of a conserved group of CCR-like genes involved in the defense response, and with the potential to alter lignin content without affecting development.

  19. Immunity to community: what can immune pathways tell us about disease patterns in corals?

    Science.gov (United States)

    Mydlarz, L. D.; Fuess, L.; Pinzon, J. C.; Weil, E.

    2016-02-01

    Predicting species composition and abundances is one of the most fundamental questions in ecology. This question is even more pressing in marine ecology and coral reefs since communities are changing at a rapid pace due to climate-related changes. Increases in disease prevalence and severity are just some of the consequences of these environmental changes. Particularly in coral reef ecosystems, diseases are increasing and driving region-wide population collapses. It has become clear, however, that not all reefs or coral species are affected by disease equally. In fact, the Caribbean is a concentrated area for diseases. The patterns in which disease manifests itself on an individual reef are also proving interesting, as not all coral species are affected by disease equally. Some species are host to different diseases, but seem to successfully fight them reducing mortality. Other species are disproportionately infected on any given reef and experience high mortality due to disease. We are interested in the role immunity can play in directing these patterns and are evaluating coral immunity using several novel approaches. We exposed 4 species of corals with different disease susceptibilities to immune stimulators and quantified of coral immunity using a combination of full transcriptome sequencing and protein activity assays for gene to phenotype analysis. We also mapped gene expression changes onto immune pathways (i.e. melanin-cascade, antimicrobial peptide synthesis, complement cascade, lectin-opsonization) to evaluate expression of immune pathways between species. In our preliminary data we found many immune genes in the disease susceptible Orbicella faveolata underwent changes in gene expression opposite of the predictions and may disply `dysfunctional' patterns of expression. We will present expression data for 4 species of coral and assess how these transcriptional and protein immune responses are related to disease susceptibility in nature, thus scaling up

  20. Erosion products in disruption simulation experiments

    International Nuclear Information System (INIS)

    Safronov, V.; Arkhipov, N.; Bakhtin, V.; Barsuk, V.; Kurkin, S.; Mironova, E.; Toporkov, D.; Vasenin, S.; Zhitlukhin, A.; Arkhipov, I.; Werle, H.; Wuerz, H.

    1998-01-01

    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 heat loads 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)

  1. 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

  2. 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

  3. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. G.; Krægpøth, Morten; Nielsen, Helena Skyt

    2015-01-01

    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...... 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...

  4. 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...... 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...

  5. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. G.; Krægpøth, Morten Visby; Skyt Nielsen, Helena

    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 schoolcohort. We...... 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...

  6. On Modelling an Immune System

    OpenAIRE

    Monroy, Raúl; Saab, Rosa; Godínez, Fernando

    2004-01-01

    Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

  7. Rebuilding immunity with Remune.

    Science.gov (United States)

    Whitfield, L

    1998-01-01

    Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response.

  8. Effects of sleep disruption and high fat intake on glucose metabolism in mice.

    Science.gov (United States)

    Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R

    2016-06-01

    Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this

  9. National Network for Immunization Information

    Science.gov (United States)

    ... American College of Obstetricians and Gynecologists . © Copyright National Network for Immunization Information. The information contained in the National Network for Immunization Information Web site should not be ...

  10. Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Ben C L van Schaijk

    Full Text Available Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use.

  11. Glaciological parameters of disruptive event analysis

    International Nuclear Information System (INIS)

    Bull, C.

    1979-01-01

    The following disruptive events caused by ice sheets are considered: continental glaciation, erosion, loading and subsidence, deep ground water recharge, flood erosion, isostatic rebound rates, melting, and periodicity of ice ages

  12. Disruptive Innovation in Chinese and Indian Businesses

    DEFF Research Database (Denmark)

    markets, has made these emerging economies fertile ground for developing and applying disruptive innovations. A novel mix of key attributes distinctive from those of established technologies or business models, disruptive innovations are typically inferior, yet affordable and "good-enough" products...... or services, which originate in lower-end market segments, but later move up to compete with those provided by incumbent firms. This book sheds new light on disruptive innovations both from and for the bottom of the pyramid in China and India, from the point of view of local entrepreneurs and international...... firms seeking to operate their businesses there. It covers both the theoretical and practical implications of disruptive innovation using conceptual frameworks alongside detailed case studies, whilst also providing a comparison of conditions and strategic options in India and China. Further, unlike...

  13. Disruption mitigation studies in DIII-D

    International Nuclear Information System (INIS)

    Taylor, P.L.; Kellman, A.G.; Evans, T.E.

    1999-01-01

    Data on the discharge behavior, thermal loads, halo currents, and runaway electrons have been obtained in disruptions on the DIII-D tokamak. These experiments have also evaluated techniques to mitigate the disruptions while minimizing runaway electron production. Experiments injecting cryogenic impurity killer pellets of neon and argon and massive amounts of helium gas have successfully reduced these disruption effects. The halo current generation, scaling, and mitigation are understood and are in good agreement with predictions of a semianalytic model. Results from killer pellet injection have been used to benchmark theoretical models of the pellet ablation and energy loss. Runaway electrons are often generated by the pellets and new runaway generation mechanisms, modifications of the standard Dreicer process, have been found to explain the runaways. Experiments with the massive helium gas puff have also effectively mitigated disruptions without the formation of runaway electrons that can occur with killer pellets

  14. Runaway electron generation in tokamak disruptions

    International Nuclear Information System (INIS)

    Helander, P.; Andersson, F.; Fueloep, T.; Smith, H.; Anderson, D.; Lisak, M.; Eriksson, L.-G.

    2005-01-01

    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 filamented. It is also shown that higher runaway electron generation is expected if the thermal quench is sufficiently fast. (author)

  15. Disrupted functional brain networks in autistic toddlers

    NARCIS (Netherlands)

    Boersma, M.; Kemner, C.; Reus, M.A. de; Collin, G; Snijders, T.M.; Hofman, D.; Buitelaar, J.K.; Stam, C.J.; Heuvel, M.P. van den

    2013-01-01

    Communication and integration of information between brain regions plays a key role in healthy brain function. Conversely, disruption in brain communication may lead to cognitive and behavioral problems. Autism is a neurodevelopmental disorder that is characterized by impaired social interactions

  16. Integrated disruption avoidance and mitigation in KSTAR

    International Nuclear Information System (INIS)

    Kim, Jayhyun; Woo, M.H.; Han, H.; In, Y.; Bak, J.G.; Eidietis, N.W.

    2014-01-01

    The final target of Korea Superconducting Tokamak Advanced Research (KSTAR) aims advanced tokamak operation at plasma current 2 MA and toroidal field 3.5 T. In order to safely achieve the target, disruption counter-measures are unavoidable when considering the disruption risks, inevitably accompanied with high performance discharges, such as electro-magnetic load on conducting structures, collisional damage by run-away electrons, and thermal load on plasma facing components (PFCs). In this reason, the establishment of integrated disruption mitigation system (DMS) has been started for routine mega-ampere class operations of KSTAR since 2013 campaign. The DMS mainly consists of the disruption prediction and its avoidance/mitigation in company with logical/technical integration of them. We present the details of KSTAR DMS and the related experimental results in this article. (author)

  17. 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 discuss...... the three main subproblems in railway disruption management: timetable adjustment, and rolling stock and crew re-scheduling. Next to a general description of these problems, we give an overview of the existing literature and we present some details of the specific situations at DSB S-tog and NS....... These are the railway operators in the suburban area of Copenhagen, Denmark, and on the main railway lines in the Netherlands, respectively. Since not much research has been carried out yet on Operations Research models for disruption management in the railway context, models and techniques that have been developed...

  18. 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...

  19. Emergency Management involving Critical Infrastructure Disruptions: operationalizing the deployment of resilience capabilities

    DEFF Research Database (Denmark)

    Trucco, P.; Petrenj, B.; Kozin, Igor

    2016-01-01

    , and/or rapidly recover from a potentially disruptive event. The study proposes a novel approach to integrating the resilience capacities of CI into the EM cycle, which facilitates emergency services and CI operators to collaborate in addressing resilience improvement measures, while planning to cope...... with CI disruptions. It grounds on a previously published comprehensive framework which reflects the main characteristics of such emergencies (e.g. interdependent, multi-sectoral, multi-stakeholder) and supports the identification, assessment and development of specific technical and organizational...

  20. Immunity: Insect Immune Memory Goes Viral.

    Science.gov (United States)

    Ligoxygakis, Petros

    2017-11-20

    Adaptive memory in insect immunity has been controversial. In this issue, Andino and co-workers propose that acquisition of viral sequences in the host genome gives rise to anti-sense, anti-viral piRNAs. Such sequences can be regarded as both a genomic archive of past infections and as an armour of potential heritable memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Treatment of Osteomyelitis: A Case for Disruption of the Affected Adjacent Periosteum.

    Science.gov (United States)

    Hudson, John W; Daly, Austin P; Foster, Michael

    2017-10-01

    To evaluate the response of mandibular osteomyelitis treated by surgical decortication with disruption of the affected adjacent periosteum in concert with long-term targeted antibiotic therapy. The hypothesis is that, by removing the buccal cortical plate and disrupting the hypertrophically inflamed adjacent periosteum, the medullary bone will be brought in contact with bleeding tissue and circulating immunologic factors and antibiotics, which will promote definitive resolution. A retrospective review was conducted of 7 patient charts with associated radiographs from November 2010 to August 2016 treated by the first author at the University of Tennessee Medical Center (Knoxville, TN). Patients with chronic suppurative or nonsuppurative osteomyelitis of the mandible without condylar involvement or pathologic fracture were selected and treated with decortication with periosteal disruption in combination with long-term targeted antibiotic therapy. Seven patients (3 women and 4 men; mean age, 60 yr) underwent decortication with periosteal disruption of the affected area and received at least 6 weeks of targeted intravenous antibiotics. Computed tomography was performed preoperatively and a repeat study was performed after completion of antibiotics. In each case, post-treatment imaging showed definitive resolution after treatment with decortication in concert with disruption of the inflamed hypertrophic periosteum and intravenous antibiotics. Debridement of the infected cortical bone with restoration of the blood supply through disruption of the adjacent periosteum provided definitive resolution of mandibular osteomyelitis in the 7 patients treated. The hypothesis is that disruption of the affected adjacent periosteum reintroduces an immune-mediated response in concert with improved antibiotic delivery to and penetrance of the diseased mandible, aiding in definitive resolution. Decortication with periosteal disruption allows for preservation of the inferior alveolar

  2. Resonant Tidal Disruption in Galactic Nuclei

    OpenAIRE

    Rauch, Kevin P.; Ingalls, Brian

    1997-01-01

    It has recently been shown that the rate of angular momentum relaxation in nearly-Keplerian star clusters is greatly increased by a process termed resonant relaxation (Rauch & Tremaine 1996), who also argued that tidal disruption of stars in galactic nuclei containing massive black holes could be noticeably enhanced by this process. We describe here the results of numerical simulations of resonant tidal disruption which quantitatively test the predictions made by Rauch & Tremaine. The simulat...

  3. Disruptions, loads, and dynamic response of ITER

    International Nuclear Information System (INIS)

    Nelson, B.; Riemer, B.; Sayer, R.; Strickler, D.; Barabaschi, P.; Ioki, K.; Johnson, G.; Shimizu, K.; Williamson, D.

    1995-01-01

    Plasma disruptions and the resulting electromagnetic loads are critical to the design of the vacuum vessel and in-vessel components of the International Thermonuclear Experimental Reactor (ITER). This paper describes the status of plasma disruption simulations and related analysis, including the dynamic response of the vacuum vessel and in-vessel components, stresses and deflections in the vacuum vessel, and reaction loads in the support structures

  4. BUSINESS MODEL PATTERNS FOR DISRUPTIVE TECHNOLOGIES

    OpenAIRE

    BENJAMIN AMSHOFF; CHRISTIAN DÜLME; JULIAN ECHTERFELD; JÜRGEN GAUSEMEIER

    2015-01-01

    Companies nowadays face a myriad of business opportunities as a direct consequence of manifold disruptive technology developments. As a basic characteristic, disruptive technologies lead to a severe shift in value-creation networks giving rise to new market segments. One of the key challenges is to anticipate the business logics within these nascent and formerly unknown markets. Business model patterns promise to tackle this challenge. They can be interpreted as proven business model elements...

  5. The influence of a conducting wall on disruptions in HBT-EP

    International Nuclear Information System (INIS)

    Kombargi, R.

    1997-01-01

    The characteristics of long wavelength magnetohydrodynamic (MHD) disruptive instabilities have been studied in a tokamak device with segmented and movable conducting walls. Coupling between the wall and the plasma was varied by systematically adjusting the radial position, b, of the conducting plates relative to the plasma surface of minor radius a. By pre-selecting the total plasma current ramp rate (dI p /dt), disruptive instabilities driven either by large edge currents or high plasma pressure were studied. Specifically, three types of disruptions caused by both external (to the plasma) and internal instabilities were obtained by changing the plasma-wall separation (b/a) and the temporal evolution of the total plasma current. The properties of these disruptions were examined using a variety of magnetic pickup coils and arrays of soft x-ray detectors. Experiments demonstrated that rapidly developing, low-n kink instabilities were suppressed if the conducting wall was positioned sufficiently near the plasma (b/a p /dt > 0) was maintained. Conducting wall stabilization of fast growing external instabilities was observed in discharges with high edge current and in plasmas with β-values near the ideal MED stability boundary. When the conducting wall was near the plasma surface and as the current profile evolved in time (dI p /dt < 0), slowly growing internal instabilities would also lead to disruptions. Disruption mechanisms for plasmas with b/a=1.52 and b/a=1.07 were compared. Differences in the precursor modes, the speed of the thermal collapse and the chronological sequence of events were found. In summary, the disruptions with an external character were eliminated when the conducting wall was moved from b/a=1.52 to b/a<1.2. Internal disruptions could not be averted even with b/a=1.07

  6. Cationic peptide exposure enhances pulsed-electric-field-mediated membrane disruption.

    Science.gov (United States)

    Kennedy, Stephen M; Aiken, Erik J; Beres, Kaytlyn A; Hahn, Adam R; Kamin, Samantha J; Hagness, Susan C; Booske, John H; Murphy, William L

    2014-01-01

    The use of pulsed electric fields (PEFs) to irreversibly electroporate cells is a promising approach for destroying undesirable cells. This approach may gain enhanced applicability if the intensity of the PEF required to electrically disrupt cell membranes can be reduced via exposure to a molecular deliverable. This will be particularly impactful if that reduced PEF minimally influences cells that are not exposed to the deliverable. We hypothesized that the introduction of charged molecules to the cell surfaces would create regions of enhanced transmembrane electric potential in the vicinity of each charged molecule, thereby lowering the PEF intensity required to disrupt the plasma membranes. This study will therefore examine if exposure to cationic peptides can enhance a PEF's ability to disrupt plasma membranes. We exposed leukemia cells to 40 μs PEFs in media containing varying concentrations of a cationic peptide, polyarginine. We observed the internalization of a membrane integrity indicator, propidium iodide (PI), in real time. Based on an individual cell's PI fluorescence versus time signature, we were able to determine the relative degree of membrane disruption. When using 1-2 kV/cm, exposure to >50 μg/ml of polyarginine resulted in immediate and high levels of PI uptake, indicating severe membrane disruption, whereas in the absence of peptide, cells predominantly exhibited signatures indicative of no membrane disruption. Additionally, PI entered cells through the anode-facing membrane when exposed to cationic peptide, which was theoretically expected. Exposure to cationic peptides reduced the PEF intensity required to induce rapid and irreversible membrane disruption. Critically, peptide exposure reduced the PEF intensities required to elicit irreversible membrane disruption at normally sub-electroporation intensities. We believe that these cationic peptides, when coupled with current advancements in cell targeting techniques will be useful tools in

  7. HIV and Immunizations

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV and Immunizations Last Reviewed: February 6, 2018 Key ...

  8. Immunity to parasitic infection

    National Research Council Canada - National Science Library

    Lamb, Tracey J

    2012-01-01

    .... Often endemic in developing countries many parasitic diseases are neglected in terms of research funding and much remains to be understood about parasites and the interactions they have with the immune system...

  9. Exercise and immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007165.htm Exercise and immunity To use the sharing features on ... take a daily walk or follow a simple exercise routine a few times a week. Exercise helps ...

  10. Adults Need Immunizations, Too!

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Andrew Kroger from CDC’s National Center for Immunization and Respiratory Diseases discusses simple, safe, and effective ways adults can help protect themselves, their family, and their community from serious and deadly diseases.

  11. [Exosomes and Immune Cells].

    Science.gov (United States)

    Seo, Naohiro

    2017-05-01

    In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation. Thus, immune cells produce functional exosomes in the activation state- and/or differentiation stage-dependent manner. In this review, the role of immune cell-derived exosomes will be introduced, focusing mainly on immune reaction against tumor.

  12. Immune responses to metastases

    International Nuclear Information System (INIS)

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  13. Immunity of international organizations

    CERN Document Server

    Schrijver, Nico

    2015-01-01

    Immunity rules are part and parcel of the law of international organizations. It has long been accepted that international organizations and their staff need to enjoy immunity from the jurisdiction of national courts. However, it is the application of these rules in practice that increasingly causes controversy. Claims against international organizations are brought before national courts by those who allegedly suffer from their activities. These can be both natural and legal persons such as companies. National courts, in particular lower courts, have often been less willing to recognize the immunity of the organization concerned than the organization s founding fathers. Likewise, public opinion and legal writings frequently criticize international organizations for invoking their immunity and for the lack of adequate means of redress for claimants. It is against this background that an international conference was organized at Leiden University in June 2013. A number of highly qualified academics and practit...

  14. Vaccines and immunization

    African Journals Online (AJOL)

    Prof Ezechukwu

    vaccines for malaria and HIV infection. Despite the ... decades, effective vaccines against the major causes of ... challenge antibodies, specific helper and effector T lymphocytes ... materials to produced immunity to a disease. It was originally ...

  15. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  16. 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.

  17. 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 ...... 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.......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......, to be able to detect effects and predict mixture effects. In addition, a new hypothesis have emerge concerning a potential role of exposure to endocrine disrupting chemicals, and the development of obesity and obesity related diseases. AIM: This PhD project aimed to gain more information regarding...

  18. Disruption modeling in support of ITER

    International Nuclear Information System (INIS)

    Bandyopadhyay, I.

    2015-01-01

    Plasma current disruptions and Vertical Displacement Events (VDEs) are one of the major concerns in any tokamak as they lead to large electromagnetic forces to tokamak first wall components and vacuum vessel. Their occurrence also means disruption to steady state operations of tokamaks. Thus future fusion reactors like ITER must ensure that disruptions and VDEs are minimized. However, since there is still finite probability of their occurrence, one must be able to characterize disruptions and VDEs and able to predict, for example, the plasma current quench time and halo current amplitude, which mainly determine the magnitude of the electromagnetic forces. There is a concerted effort globally to understand and predict plasma and halo current evolution during disruption in tokamaks through MHD simulations. Even though Disruption and VDEs are often 3D MHD perturbations in nature, presently they are mostly simulated using 2D axisymmetric MHD codes like the Tokamak Simulation Code (TSC) and DINA. These codes are also extensively benchmarked against experimental data in present day tokamaks to improve these models and their ability to predict these events in ITER. More detailed 3D models like M3D are only recently being developed, but they are yet to be benchmarked against experiments, as also they are massively computationally exhaustive

  19. Immunization in pregnancy.

    Science.gov (United States)

    Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

    2009-11-01

    To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed

  20. Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study.

    Science.gov (United States)

    Lankelma, Jacqueline M; Cranendonk, Duncan R; Belzer, Clara; de Vos, Alex F; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

    2017-09-01

    The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens. As such, the use of antibiotics may attribute to immunosuppression as seen in sepsis. We aimed to test whether disruption of the gut microbiota affects systemic innate immune responses during endotoxemia in healthy subjects. In this proof-of-principle intervention trial, 16 healthy young men received either no treatment or broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days, after which all were administered lipopolysaccharide intravenously to induce a transient sepsis-like syndrome. At various time points, blood and faeces were sampled. Gut microbiota diversity was significantly lowered by the antibiotic treatment in all subjects. Clinical parameters, neutrophil influx, cytokine production, coagulation activation and endothelial activation during endotoxemia were not different between antibiotic-pretreated and control individuals. Antibiotic treatment had no impact on blood leucocyte responsiveness to various Toll-like receptor ligands and clinically relevant causative agents of sepsis ( Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli ) during endotoxemia. These findings suggest that gut microbiota disruption by broad-spectrum antibiotics does not affect systemic innate immune responses in healthy subjects during endotoxemia in humans, disproving our hypothesis. Further research is needed to test this hypothesis in critically ill patients. These data underline the importance of translating findings in mice to humans. ClinicalTrials.gov (NCT02127749; Pre-results). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  1. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  2. Adults Need Immunizations, Too!

    Centers for Disease Control (CDC) Podcasts

    2012-03-19

    In this podcast, Dr. Andrew Kroger from CDC’s National Center for Immunization and Respiratory Diseases discusses simple, safe, and effective ways adults can help protect themselves, their family, and their community from serious and deadly diseases.  Created: 3/19/2012 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 3/19/2012.

  3. Immune dysfunction in cirrhosis

    Science.gov (United States)

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  4. Immunity to Fish Rhabdoviruses

    OpenAIRE

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabd...

  5. Single-cell technologies to study the immune system.

    Science.gov (United States)

    Proserpio, Valentina; Mahata, Bidesh

    2016-02-01

    The immune system is composed of a variety of cells that act in a coordinated fashion to protect the organism against a multitude of different pathogens. The great variability of existing pathogens corresponds to a similar high heterogeneity of the immune cells. The study of individual immune cells, the fundamental unit of immunity, has recently transformed from a qualitative microscopic imaging to a nearly complete quantitative transcriptomic analysis. This shift has been driven by the rapid development of multiple single-cell technologies. These new advances are expected to boost the detection of less frequent cell types and transient or intermediate cell states. They will highlight the individuality of each single cell and greatly expand the resolution of current available classifications and differentiation trajectories. In this review we discuss the recent advancement and application of single-cell technologies, their limitations and future applications to study the immune system. © 2015 The Authors. Immunology Published by John Wiley & Sons Ltd.

  6. 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

  7. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  8. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  9. Immune Reconstitution Inflammatory Syndrome (IRIS): What pathologists should know.

    Science.gov (United States)

    Nelson, Ann Marie; Manabe, Yukari C; Lucas, Sebastian B

    2017-07-01

    Antiretroviral therapy has significantly improved the quality and length of life for those patients able to access effective and sustained treatment. The resulting restoration of the immune response is associated with a change in the clinical presentation of opportunistic infections, and the histologic reaction to pathogens. A complex combination of alterations in host response across the stages of HIV infection has been documented over the past 3 decades. The defects are seen in both acute and chronic phases of inflammation and involve innate and adaptive immunity. In advanced stages of HIV infection, the marked disruption of lymphoid tissue and loss of follicular dendritic cells limits the host's ability to process antigen and mount specific responses to pathogens. There are qualitative and quantitative defects in CD4 T cells due to HIV infection. The resulting indirect effects include loss of cytokine production, dysregulation of B-cell function, loss of cellular mediated immunity and "holes" in the immunologic repertoire that may not be restored with the use of antiretroviral therapy. Immune reconstitution allows the host to respond to and control infection, but a significant number of patients will have atypical inflammatory syndromes during the recovery period. We briefly discuss the impact of HIV infection on the immune system and give an overview of the spectrum of conditions attributed to the Immune Reconstitution Inflammatory syndrome (IRIS). Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Escaping deleterious immune response in their hosts: lessons from trypanosomatids

    Directory of Open Access Journals (Sweden)

    Anne eGeiger

    2016-05-01

    Full Text Available The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, T. cruzi and Leishmania spp are important human pathogens causing Human African Trypanosomiasis (HAT or Sleeping Sickness, Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs or sandflies and affect millions of people worldwide.In humans, extracellular African trypanosomes (T. brucei evade the hosts’ immune defences, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response.This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and, will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation.

  11. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    Science.gov (United States)

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  12. Gas jet disruption mitigation studies on Alcator C-Mod

    International Nuclear Information System (INIS)

    Granetz, R.; Whyte, D.G.; Izzo, V.A.; Biewer, T.; Reinke, M.L.; Terry, J.; Bader, A.; Bakhtiari, M.; Jernigan, T.; Wurden, G.

    2006-01-01

    Damaging effects of disruptions are a major concern for Alcator C-Mod, ITER and future tokamak reactors. High-pressure noble gas jet injection is a mitigation technique which potentially satisfies the operational requirements of fast response time and reliability, while still being benign to subsequent discharges. Disruption mitigation experiments using an optimized gas jet injection system are being carried out on Alcator C-Mod to study the physics of gas jet penetration into high pressure plasmas, as well as the ability of the gas jet impurities to convert plasma energy into radiation on timescales consistent with C-Mod's fast quench times, and to reduce halo currents given C-Mod's high-current density. The dependence of impurity penetration and effectiveness on noble gas species (He, Ne, Ar, Kr) is also being studied. It is found that the high-pressure neutral gas jet does not penetrate deeply into the C-Mod plasma, and yet prompt core thermal quenches are observed on all gas jet shots. 3D MHD modelling of the disruption physics with NIMROD shows that edge cooling of the plasma triggers fast growing tearing modes which rapidly produce a stochastic region in the core of the plasma and loss of thermal energy. This may explain the apparent effectiveness of the gas jet in C-Mod despite its limited penetration. The higher-Z gases (Ne, Ar, Kr) also proved effective at reducing halo currents and decreasing thermal deposition to the divertor surfaces. In addition, noble gas jet injection proved to be benign for plasma operation with C-Mod's metal (Mo) wall, actually improving the reliability of the startup in the following discharge

  13. Nonlinear disruption of ecological interactions in response to nitrogen deposition.

    Science.gov (United States)

    Ochoa-Hueso, Raúl

    2016-10-01

    Global environmental change (GEC) is affecting species interactions and causing a rapid decline in biodiversity. In this study, I present a new Ecosystem Disruption Index to quantify the impacts of simulated nitrogen (N) deposition (0, 10, 20, and 50 kg N·ha -1 ·yr -1  + 6-7 kg N·ha -1 ·yr -1 background) on abiotic and biotic ecological interactions. This comparative index is based on pairwise linear and quadratic regression matrices. These matrices, calculated at the N treatment level, were constructed using a range of abiotic and biotic ecosystem constituents: soil pH, shrub cover, and the first component of several separate principal component analyses using soil fertility data (total carbon and N) and community data (annual plants, microorganisms, biocrusts, edaphic fauna) for a total of seven ecosystem constituents. Four years of N fertilization in a semiarid shrubland completely disrupted the network of ecological interactions, with a greater proportional increase in ecosystem disruption at low N addition levels. Biotic interactions, particularly those involving microbes, shrubs, and edaphic fauna, were more prone to be lost in response to N, whereas interactions involving soil properties were more resilient. In contrast, edaphic fauna was the only group directly affected by N addition, with mites and collembolans increasing their abundance with up to 20 kg N·ha -1 ·yr -1 and then decreasing, which supports the idea of higher-trophic-level organisms being more sensitive to disturbance due to more complex links with other ecosystem constituents. Future experimental studies evaluating the impacts of N deposition, and possibly other GEC drivers, on biodiversity and biotic and abiotic interactions may be able to explain results more effectively in the context of ecological networks as a key feature of ecosystem sensitivity. © 2016 by the Ecological Society of America.

  14. U.S. Immunization program adult immunization activities and resources

    Science.gov (United States)

    Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

    2016-01-01

    ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve

  15. Interplay between intrinsic plasma rotation and magnetic island evolution in disruptive discharges

    Energy Technology Data Exchange (ETDEWEB)

    Ronchi, G.; Severo, J. H. F. [Universidade de São Paulo, Instituto de Física (Brazil); Salzedas, F. [Universidade do Porto, Faculdade de Engenharia (Portugal); Galvão, R. M. O., E-mail: rgalvao@if.usp.br; Sanada, E. K. [Universidade de São Paulo, Instituto de Física (Brazil)

    2016-05-15

    The behavior of the intrinsic toroidal rotation of the plasma column during the growth and eventual saturation of m/n = 2/1 magnetic islands, triggered by programmed density rise, has been carefully investigated in disruptive discharges in TCABR. The results show that, as the island starts to grow and rotate at a speed larger than that of the plasma column, the angular frequency of the intrinsic toroidal rotation increases and that of the island decreases, following the expectation of synchronization. As the island saturates at a large size, just before a major disruption, the angular speed of the intrinsic rotation decreases quite rapidly, even though the island keeps still rotating at a reduced speed. This decrease of the toroidal rotation is quite reproducible and can be considered as an indicative of disruption.

  16. Axisymmetric disruption dynamics including current profile changes in the ASDEX-Upgrade tokamak

    International Nuclear Information System (INIS)

    Nakamura, Y.; Pautasso, G.; Gruber, O.; Jardin, S.C.

    2002-01-01

    Axisymmetric MHD simulations have revealed a new driving mechanism that governs the vertical displacement event (VDE) dynamics in tokamak disruptions. A rapid flattening of the plasma current profile during the disruption plays a substantial role in dragging a single null-diverted plasma vertically towards the divertor. As a consequence, the occurrence of downward-going VDEs predominates over the upward-going ones in bottom-diverted discharges. This dragging effect, due to an abrupt change in the current profile, is absent in up-down symmetric limiter discharges. These simulation results are consistent with experiments in ASDEX-Upgrade. Together with the attractive force that arises from passive shell currents induced by the plasma current quench, the dragging effect explains many details of the VDE dynamics over the whole period of the disruptive termination. (author)

  17. Modeling of thermal effects on TIBER II divertor during plasma disruptions

    International Nuclear Information System (INIS)

    Bruhn, M.L.; Perkins, L.J.

    1987-01-01

    Mapping the disruption power flow from the mid-plane of the TIBER Engineering Test Reactor to its divertor and calculating the resulting thermal effects are accomplished through the modification and coupling of three presently existing computer codes. The resulting computer code TADDPAK (Thermal Analysis Divertor during Disruption PAcKage) provides three-dimensional graphic presentations of time and positional dependent thermal effects on a poloidal cross section of the double-null-divertor configured reactor. These thermal effects include incident heat flux, surface temperature, vaporization rate, total vaporization, and melting depth. The dependence of these thermal effects on material choice, disruption pulse shape, and the characteristic thickness of the plasma scrape-off layer is determined through parametric analysis with TADDPAK. This computer code is designed to be a convenient, rapid, and user-friendly modeling tool which can be easily adapted to most tokamak double-null-divertor reactor designs

  18. The immune self: a selectionist theory of recognition, learning, and remembering within the immune system.

    Science.gov (United States)

    Kradin, R L

    1995-01-01

    In this paper, I have briefly explored metaphors shared by the immune and nervous systems and shown that this exercise can lead to the elucidation of common principles of organization, as well as to predictions concerning how the immune system functions. Metaphor itself undoubtedly reflects the way in which we categorize and retrieve information 44], so it is not surprising that the deep processes of language tend to sample information from related data categories. Although the nervous and immune systems are obviously not the same and metaphors are indeed just that, my primary goal has been to suggest that by virtue of their having evolved in parallel over millions of years, the nervous and immune systems currently use the same archetypal principles and strategies to address related challenges in information processing and retrieval. Ultimately, nature is conservative. One need only look at a tree, a river, the airways, or the vascular bed in order to see how a fractal pattern of repetitive dichotomous branching has been used by each, in order to optimize the transport of fluids over large distances [45]. While each system has had to adopt different materials in order to solve the problem, the shape of their solutions is remarkably alike. In the immune and nervous systems, the elements used to produce optimal functional responses are also quite different, but again the solutions have been achieved by comparable strategies. I am certain that these two great systems of information processing, each responding with vastly different kinetics, will prove to be far more integrally interdependent than has been previously recognized. For example, should a swift response by the immune system be required in an overwhelming invasion by microbial pathogens, the immune system may be able to cooperate with the rapidly reacting nervous system to rid the host of the invaders. In this regard, we have shown that the beta-adrenergic hormone epinephrine rapidly increases the traffic of

  19. Two-dimensional disruption thermal analysis code DREAM

    International Nuclear Information System (INIS)

    Yamazaki, Seiichiro; Kobayashi, Takeshi; Seki, Masahiro.

    1988-08-01

    When a plasma disruption takes place in a tokamak type fusion reactor, plasma facing components such as first wall and divertor/limiter are subjected to an intense heat load with very high heat flux and 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 (melting/evaporation) and radiation heat loss is required in the design of these components. This paper describes the computer code DREAM developed to perform the two-dimensional transient thermal analysis that takes phase changes and radiation into account. The input and output of the code and a sample analysis on a disruption simulation experiment are also reported. The user's input manual is added as an appendix. The profiles and time variations of temperature, and melting and evaporated thicknesses of the material subjected to intense heat load can be obtained, using this computer code. This code also gives the temperature data for elastoplastic analysis with FEM structural analysis codes (ADINA, MARC, etc.) to evaluate the thermal stress and crack propagation behavior within the wall materials. (author)

  20. Impact of Disruptive Innovations on Mobile Telecom Industry in Lebanon

    Directory of Open Access Journals (Sweden)

    Wael Bakhit

    2016-04-01

    Full Text Available The telecommunication industry is different from other industries in the basis of innovation rate. This industry continuously provides end users with new technological generations and disruptive technologies. Due to the complexity of the nature of the product served, telecommunication industry is an important case to study in order to explain the real reasons for the challenges facing telecom companies. Researching in this area will explain why some companies survive while others fail. The wide range served technology innovations is most likely to result in rapid mutation of consumers’ spending habits thus directly influencing the mobile phone companies. The aim of this is to test the reliability of innovations and its impact on companies’ profitability. For that purpose, a survey with 200 end users and 20 employees from two telecom providers (“Alfa, and “Touch” was conducted to investigate various disruptive and conventional means and their impact on the financial performance of telecom industry. The results show that most of the revenue of telecom industry comes from usage of data while the industry is lacking for competition, and quality services while charging high tariffs for customers. Currently customers are migrating to data, therefore performing a pressure on the industry to improve its services. To conclude, network operators need to decide what to they want to sacrifice and how far they want to go to reach targeted results.

  1. Local and integral disruption forces on the tokamak wall

    Science.gov (United States)

    Pustovitov, V. D.; Kiramov, D. I.

    2018-04-01

    The disruption-induced forces on the tokamak wall are evaluated analytically within the standard large-aspect-ratio model that implies axisymmetry, circular plasma and wall, and absence of halo currents. Additionally, the ideal-wall reaction is assumed. The disruptions are modelled as rapid changes in the plasma pressure (thermal quench (TQ)) and net current (current quench (CQ)). The force distribution over the poloidal angle is found as a function of these inputs. The derived formulas allow comparison of the TQ- and CQ-produced forces calculated differently, with and without account of the poloidal current induced in the wall. The latter variant represents the inherent property of the codes treating the wall as a set of toroidal filaments. It is proved here that such a simplification leads to unacceptably large errors in the simulated forces for both TQs and CQs. It is also shown that the TQ part of the force must prevail over that due to CQ in the high-β scenarios developed for JT-60SA and ITER.

  2. Filoviral Immune Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Christopher F. Basler

    2011-09-01

    Full Text Available The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV and Marburgvirus (MARV, causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN response is critical for establishing an antiviral state in the host cell and subsequent activation of the adaptive immune responses. Several filoviral encoded components target Type I IFN responses, and this innate immune suppression is important for viral replication and pathogenesis. For example, EBOV VP35 inhibits the phosphorylation of IRF-3/7 by the TBK-1/IKKε kinases in addition to sequestering viral RNA from detection by RIG-I like receptors. MARV VP40 inhibits STAT1/2 phosphorylation by inhibiting the JAK family kinases. EBOV VP24 inhibits nuclear translocation of activated STAT1 by karyopherin-α. The examples also represent distinct mechanisms utilized by filoviral proteins in order to counter immune responses, which results in limited IFN-α/β production and downstream signaling.

  3. Immune memory in invertebrates.

    Science.gov (United States)

    Milutinović, Barbara; Kurtz, Joachim

    2016-08-01

    Evidence for innate immune memory (or 'priming') in invertebrates has been accumulating over the last years. We here provide an in-depth review of the current state of evidence for immune memory in invertebrates, and in particular take a phylogenetic viewpoint. Invertebrates are a very heterogeneous group of animals and accordingly, evidence for the phenomenon of immune memory as well as the hypothesized molecular underpinnings differ largely for the diverse invertebrate taxa. The majority of research currently focuses on Arthropods, while evidence from many other groups of invertebrates is fragmentary or even lacking. We here concentrate on immune memory that is induced by pathogenic challenges, but also extent our view to a non-pathogenic context, i.e. allograft rejection, which can also show forms of memory and can inform us about general principles of specific self-nonself recognition. We discuss definitions of immune memory and a number of relevant aspects such as the type of antigens used, the route of exposure, and the kinetics of reactions following priming. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Jet disruption in wide-angle tailed radio galaxies

    International Nuclear Information System (INIS)

    Burns, J.O.; Norman, M.L.; Clarke, D.A.

    1986-01-01

    The mechanisms responsible for the bending of the jets and tails of wide-angle tailed (WAT) radio galaxies in clusters are investigated theoretically, with a focus on sharp bends and rapid jet disruption. Large (1 Mpc) and small (200 kpc) WATs are differentiated, and it is suggested that the jet-tail transition in large WATs is due to collisions between the jet and cool clouds of the intracluster medium (ICM). The transition in small WATs is attributed to the passage of the jet through a planar Mach disk perpendicular to the jet flow direction. Such a disk is shown in numerical simulations to form when there is a shocklike jump in ambient pressure at the ISM/ICM interface; the origins of such a jump are explored. 14 references

  6. Disruption Mitigation System Developments and Design for ITER

    Energy Technology Data Exchange (ETDEWEB)

    Baylor, Larry R. [ORNL; Barbier, Charlotte N. [ORNL; Bull, Nora D. [ORNL; Combs, Stephen Kirk [ORNL; Fisher, Paul W. [ORNL; Kiss, Gabor [ITER Organization, Cadarache, France; Ericson, Milton Nance [ORNL; Wilgen, John B. [ORNL; Maruyama, So [ITER Organization, Cadarache, France; Meitner, Steven J. [ORNL; Lyttle, Mark S. [ORNL; Rasmussen, David A. [ORNL; Carmichael, Justin R. [ORNL; Smith, Stephen Fulton [ORNL

    2015-09-01

    A disruption mitigation system (DMS) is under design for ITER to inject sufficient material deeply into the plasma for rapid plasma thermal shutdown and collisional suppression of any resulting runaway electrons. Progress on the development and design of both a shattered pellet injector (SPI) that produces large solid cryogenic pellets to provide reliable deep penetration of material and a fast opening high flow rate gas valve for massive gas injection (MGI) is presented. Cryogenic pellets of deuterium and neon up to 25 mm in size have been formed and accelerated with a prototype injector and a full scale prototype MGI valve is now in testing. Implications of the design with respect to response time and reliability at the proposed injector locations on ITER are discussed.

  7. Heterosubtypic immunity to influenza A virus infections in mallards may explain existence of multiple virus subtypes.

    Directory of Open Access Journals (Sweden)

    Neus Latorre-Margalef

    Full Text Available Wild birds, particularly duck species, are the main reservoir of influenza A virus (IAV in nature. However, knowledge of IAV infection dynamics in the wild bird reservoir, and the development of immune responses, are essentially absent. Importantly, a detailed understanding of how subtype diversity is generated and maintained is lacking. To address this, 18,679 samples from 7728 Mallard ducks captured between 2002 and 2009 at a single stopover site in Sweden were screened for IAV infections, and the resulting 1081 virus isolates were analyzed for patterns of immunity. We found support for development of homosubtypic hemagglutinin (HA immunity during the peak of IAV infections in the fall. Moreover, re-infections with the same HA subtype and related prevalent HA subtypes were uncommon, suggesting the development of natural homosubtypic and heterosubtypic immunity (p-value = 0.02. Heterosubtypic immunity followed phylogenetic relatedness of HA subtypes, both at the level of HA clades (p-value = 0.04 and the level of HA groups (p-value = 0.05. In contrast, infection patterns did not support specific immunity for neuraminidase (NA subtypes. For the H1 and H3 Clades, heterosubtypic immunity showed a clear temporal pattern and we estimated within-clade immunity to last at least 30 days. The strength and duration of heterosubtypic immunity has important implications for transmission dynamics of IAV in the natural reservoir, where immune escape and disruptive selection may increase HA antigenic variation and explain IAV subtype diversity.

  8. 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

  9. Heat load material studies: Simulated tokamak disruptions

    International Nuclear Information System (INIS)

    Gahl, J.M.; McDonald, J.M.; Zakharov, A.; Tserevitinov, S.; Barabash, V.; Guseva, M.

    1991-01-01

    It is clear that an improved understanding of the effects of tokamak disruptions on plasma facing component materials is needed for the ITER program. very large energy fluxes are predicted to be deposited in ITER and could be very damaging to the machine. During 1991, Sandia National Laboratories and the University of New Mexico conducted cooperative tokamak disruption simulation experiments at several Soviet facilities. These facilities were located at the Efremov Institute in Leningrad, the Kurchatov Atomic Energy Institute (Troisk and Moscow) and the Institute for Physical Chemistry of the Soviet Adademy of Sciences in Moscow. Erosion of graphite from plasma stream impact is seen to be much less than that observed with laser or electron beams with similar energy fluxes. This, along with other data obtained, seem to suggest that the ''vapor shielding'' effect is a very important phenomenon in the study of graphite erosion during tokamak disruption

  10. Maternal Characteristics Predicting Young Girls’ Disruptive Behavior

    Science.gov (United States)

    van der Molen, Elsa; Hipwell, Alison E.; Vermeiren, Robert; Loeber, Rolf

    2011-01-01

    Little is known about the relative predictive utility of maternal characteristics and parenting skills on the development of girls’ disruptive behavior. The current study used five waves of parent and child-report data from the ongoing Pittsburgh Girls Study to examine these relationships in a sample of 1,942 girls from age 7 to 12 years. Multivariate Generalized Estimating Equation (GEE) analyses indicated that European American race, mother’s prenatal nicotine use, maternal depression, maternal conduct problems prior to age 15, and low maternal warmth explained unique variance. Maladaptive parenting partly mediated the effects of maternal depression and maternal conduct problems. Both current and early maternal risk factors have an impact on young girls’ disruptive behavior, providing support for the timing and focus of the prevention of girls’ disruptive behavior. PMID:21391016

  11. A model for disruption generated runaway electrons

    International Nuclear Information System (INIS)

    Russo, A.J.; Campbell, R.B.

    1993-01-01

    One of the possible consequences of disruptions in tokamaks is the generation of runaway electrons which can impact plasma facing components and cause damage, owing to high local energy deposition. This problem becomes more serious as the machine size and plasma current increase. Since large size and high currents are characteristics of proposed future machines, control of runaway generation is an important design consideration. A lumped circuit model for disruption runaway electron generation indicates that impurity concentration and type, as well as plasma motion, can strongly influence runaway behaviour. A comparison of disruption data from several runs on JET and DIII-D with model results demonstrate the effects of impurities, and plasma motion, on runaway number density and energy. The model is also applied to the calculation of runaway currents for ITER. (author). 16 refs, 13 figs

  12. Energy flow during disruptions in JET

    International Nuclear Information System (INIS)

    Paley, J.I.; Andrew, P.; Cowley, S.C.; Fundamenski, W.; Huber, A.

    2005-01-01

    Disruptions place severe limitations on the materials selected for plasma facing components in fusion devices. In a disruption, the plasma stored thermal and magnetic energy is dissipated leading to predicted power loadings in the current quench of up to 10 MW m -2 in JET. In the thermal quench very high power loads of up to 10 G Wm -2 would be expected if all the power flowed to the steady state strike points, however this is not observed. In this paper the energy balance associated with both events is investigated. The magnetic energy is found to balance well with radiated energy. Circumstantial evidence for limiter interaction during the thermal quench of plasmas in divertor configuration is presented and a possible mechanism for limiter interaction in disruptions resulting from the collapse of an internal transport barrier is discussed

  13. 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

  14. 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...... part we report on experiences from a large research and development project on airline disruption management. Within the project the first prototype of a multiple resource decision support system at the operations control center in a major airline, has been implemented....... 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...

  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...... report on experiences from a large research and development project on airline disruption management. Within the project the first prototype of a multiple resource decision support system at the operations control center in a major airline, has been implemented....... 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...

  16. Thermal deposition analysis during disruptions on DIII-D using infrared scanners

    International Nuclear Information System (INIS)

    Lee, R.L.; Hyatt, A.W.; Kellman, A.G.; Taylor, P.L.; Lasnier, C.J.

    1995-12-01

    The DIII-D tokamak generates plasma discharges with currents up to 3 MA and auxiliary input power up to 20 MW from neutral beams and 4 MW from radio frequency systems. In a disruption, a rapid loss of the plasma current and internal thermal energy occurs and the energy is deposited onto the torus graphite wall. Quantifying the spatial and temporal characteristics of the heat deposition is important for engineering and physics-related issues, particularly for designing future machines such as ITER. Using infrared scanners with a time resolution of 120 micros, measurements of the heat deposition onto the all-graphite walls of DIII-D during two types of disruptions have been made. Each scanner contains a single point detector sensitive to 8--12 microm radiation, allowing surface temperatures from 20 C to 2,000 C to be measured. A zinc selenide window that transmits in the infrared is used as the vacuum window. Views of the upper and lower divertor regions and the centerpost provide good coverage of the first wall for single and double null divertor discharges. During disruptions, the thermal energy is not deposited evenly onto the inner surface of the tokamak, but is deposited primarily in the divertor region when operating diverted discharges. Analysis of the heat deposition during a radiative collapse disruption of a 1.5 MA discharge revealed power densities of 300--350 MW/m 2 in the divertor region. During the thermal quench of the disruption, the energy deposited onto the divertor region was more than 70% of the stored thermal energy in the discharge prior to the disruption. The spatial distribution and temporal behavior of power deposition during high β disruptions will also be presented

  17. 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

  18. 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

  19. Quercetin, Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Yao Li

    2016-03-01

    Full Text Available In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

  20. Mucosal immunity to poliovirus.

    Science.gov (United States)

    Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

    2011-10-01

    The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

  1. Training and natural immunity

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund; Helge, Jørn Wulff; Richter, Erik

    2000-01-01

    these subjects were used to eliminate day-to-day variation in the immunological tests. Independently of diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK) cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell activity, either unstimulated or stimulated...... influence natural immunity, and suggest that ingestion of a fat-rich diet during training is detrimental to the immune system compared to the effect of a carbohydrate-rich diet....

  2. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Characterization of plasma current quench during disruptions at HL-2A

    Science.gov (United States)

    Zhu, Jinxia; Zhang, Yipo; Dong, Yunbo; HL-2A Team

    2017-05-01

    The most essential assumptions of physics for the evaluation of electromagnetic forces on the plasma-facing components due to a disruption-induced eddy current are characteristics of plasma current quenches including the current quench rate or its waveforms. The characteristics of plasma current quenches at HL-2A have been analyzed during spontaneous disruptions. Both linear decay and exponential decay are found in the disruptions with the fastest current quenches. However, there are two stages of current quench in the slow current quench case. The first stage with an exponential decay and the second stage followed by a rapid linear decay. The faster current quench rate corresponds to the faster movement of plasma displacement. The parameter regimes on the current quench time and the current quench rates have been obtained from disruption statistics at HL-2A. There exists no remarkable difference for distributions obtained between the limiter and the divertor configuration. This data from HL-2A provides basic data of the derivation of design criteria for a large-sized machine during the current decay phase of the disruptions.

  4. 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.)

  5. Disruption problematics in segmented blanket concepts

    International Nuclear Information System (INIS)

    Crutzen, Y.; Fantechi, S.; Farfaletti-Casali, F.

    1994-01-01

    In Tokamaks, the hostile operating environment originated by plasma disruption events requires that the first wall/blanket/shield components sustain the large induced electromagnetic (EM) forces without significant structural deformation and within allowable material stresses. As a consequence there is a need to improve the safety features of the blanket design concepts satisfying the disruption problematics and to formulate guidelines on the required internal reinforcements of the blanket components. The present paper describes the recent investigations on blanket reinforcement systems needed in order to optimize the first-wall/blanket/shield structural design for next step and commercial fusion reactors in the context of ITER, DEMO and SEAFP activities

  6. 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

  7. Manufacturing doubt about endocrine disrupter science

    DEFF Research Database (Denmark)

    Bergman, Åke; Becher, Georg; Blumberg, Bruce

    2015-01-01

    We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption......) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers...

  8. Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7

    Directory of Open Access Journals (Sweden)

    Vanessa M. D’Costa

    2015-09-01

    Full Text Available Intracellular bacterial pathogens of a diverse nature share the ability to evade host immunity by impairing trafficking of endocytic cargo to lysosomes for degradation, a process that is poorly understood. Here, we show that the Salmonella enterica type 3 secreted effector SopD2 mediates this process by binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange. Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding effectors RILP and FYCO1 and thereby disrupts host-driven regulation of microtubule motors. Our study identifies a bacterial effector capable of directly binding and thereby modulating Rab7 activity and a mechanism of endocytic trafficking disruption that may provide insight into the pathogenesis of other bacteria. Additionally, we provide a powerful tool for the study of Rab7 function, and a potential therapeutic target.

  9. Integrated Circuit Electromagnetic Immunity Handbook

    Science.gov (United States)

    Sketoe, J. G.

    2000-08-01

    This handbook presents the results of the Boeing Company effort for NASA under contract NAS8-98217. Immunity level data for certain integrated circuit parts are discussed herein, along with analytical techniques for applying the data to electronics systems. This handbook is built heavily on the one produced in the seventies by McDonnell Douglas Astronautics Company (MDAC, MDC Report E1929 of 1 August 1978, entitled Integrated Circuit Electromagnetic Susceptibility Handbook, known commonly as the ICES Handbook, which has served countless systems designers for over 20 years). Sections 2 and 3 supplement the device susceptibility data presented in section 4 by presenting information on related material required to use the IC susceptibility information. Section 2 concerns itself with electromagnetic susceptibility analysis and serves as a guide in using the information contained in the rest of the handbook. A suggested system hardening requirements is presented in this chapter. Section 3 briefly discusses coupling and shielding considerations. For conservatism and simplicity, a worst case approach is advocated to determine the maximum amount of RF power picked up from a given field. This handbook expands the scope of the immunity data in this Handbook is to of 10 MHz to 10 GHz. However, the analytical techniques provided are applicable to much higher frequencies as well. It is expected however, that the upper frequency limit of concern is near 10 GHz. This is due to two factors; the pickup of microwave energy on system cables and wiring falls off as the square of the wavelength, and component response falls off at a rapid rate due to the effects of parasitic shunt paths for the RF energy. It should be noted also that the pickup on wires and cables does not approach infinity as the frequency decreases (as would be expected by extrapolating the square law dependence of the high frequency roll-off to lower frequencies) but levels off due to mismatch effects.

  10. Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein.

    Directory of Open Access Journals (Sweden)

    Nicholas Glanville

    Full Text Available Human rhinovirus (RV infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2 capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine.

  11. Immune System and Kidney Transplantation.

    Science.gov (United States)

    Shrestha, Badri Man

    2017-01-01

    The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

  12. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  14. Molasses as a possible cause of an ''endocrine disruptive syndrome'' in calves

    Directory of Open Access Journals (Sweden)

    M.S. Masgoret

    2009-09-01

    Full Text Available During the mid 1990s a potentially serious, chronic syndrome was reported in well-managed beef and dairy herds from unrelated parts of South Africa. Farmers reported that it manifested as various combinations of decreased production, decreased weaning masses, apparent immune breakdown in previously immunocompetent animals, increased reproductive disorders, various mineral imbalances in non-deficient areas and goitre, noticeable as enlarged thyroid glands. The farmers associated this syndrome with certain batches of sugar cane molasses and molasses-based products. The syndrome was reminiscent of an ''endocrine disruptive syndrome''. The objective of this study was to evaluate the suspected endocrine disruptive effect of molasses included in cattle feed. Using existing in vitro assays, four batches of molasses syrup were screened for possible inclusion in a calf feeding trial. Two batches were selected for the trial. Thirty-two, 4- to 6-week-old, weaned Holstein bull calves were included in the single phase, three treatment, parallel design experiment. In two of the groups of calves, two different batches of molasses were included in their rations respectively. The control group was fed a ration to which no molasses was added, but which was balanced for energy and mineral content. The mass gain of the calves was recorded over the 6-month study period. The calves were clinically examined every week and clinical pathology parameters, immune responses and endocrine effects were regularly evaluated. Even though endocrine disrupting effects were detected with the in vitro screening assays, these could not be reproduced in the calves in the experiment. The two batches of molasses utilized in the calf feeding trial did not induce major differences in any of the parameters measured, with the exception of a lower mass gain in one of the molasses-fed groups (Group 1, which tended towards significance. The results of the study indicate that the two batches

  15. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2017-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  16. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  18. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  19. Fully immunized child

    DEFF Research Database (Denmark)

    Mutua, Martin Kavao; Kimani-Murage, Elizabeth; Ngomi, Nicholas

    2016-01-01

    Background: More efforts have been put in place to increase full immunization coverage rates in the last decade. Little is known about the levels and consequences of delaying or vaccinating children in different schedules. Vaccine effectiveness depends on the timing of its administration, and it ...

  20. Tick Innate Immunity.

    Czech Academy of Sciences Publication Activity Database

    Kopáček, Petr; Hajdušek, Ondřej; Burešová, Veronika; Daffre, S.

    2010-01-01

    Roč. 708, - (2010), 137-162 ISSN 0065-2598 R&D Projects: GA ČR GAP506/10/2136; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : tick * pathogen transmission * innate immunity Subject RIV: EC - Immunology Impact factor: 1.379, year: 2010

  1. A role of the adaptive immune system in glucose homeostasis.

    Science.gov (United States)

    Bronsart, Laura L; Contag, Christopher H

    2016-01-01

    The immune system, including the adaptive immune response, has recently been recognized as having a significant role in diet-induced insulin resistance. In this study, we aimed to determine if the adaptive immune system also functions in maintaining physiological glucose homeostasis in the absence of diet-induced disease. SCID mice and immunocompetent control animals were phenotypically assessed for variations in metabolic parameters and cytokine profiles. Additionally, the glucose tolerance of SCID and immunocompetent control animals was assessed following introduction of a high-fat diet. SCID mice on a normal chow diet were significantly insulin resistant relative to control animals despite having less fat mass. This was associated with a significant increase in the innate immunity-stimulating cytokines granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP1), and MCP3. Additionally, the SCID mouse phenotype was exacerbated in response to a high-fat diet as evidenced by the further significant progression of glucose intolerance. These results support the notion that the adaptive immune system plays a fundamental biological role in glucose homeostasis, and that the absence of functional B and T cells results in disruption in the concentrations of various cytokines associated with macrophage proliferation and recruitment. Additionally, the absence of functional B and T cells is not protective against diet-induced pathology.

  2. Indian Hedgehog Suppresses a Stromal Cell–Driven Intestinal Immune Response

    Directory of Open Access Journals (Sweden)

    B. Florien Westendorp

    2018-01-01

    Conclusions: We show that epithelium-derived Indian Hedgehog signals exclusively to fibroblasts in the intestine. Loss of Ihh leads to a rapid immune response with up-regulation of fibroblast-derived CXCL12, and migration of immune cells into the lamina propria.

  3. The receptor kinase FER is a RALF-regulated scaffold controlling plant immune signaling

    NARCIS (Netherlands)

    Stegmann, Martin; Monaghan, Jacqueline; Smakowska-Luzan, Elwira; Rovenich, Hanna; Lehner, Anita; Holton, Nicholas; Belkhadir, Youssef; Zipfel, Cyril

    2017-01-01

    In plants, perception of invading pathogens involves cell-surface immune receptor kinases. Here, we report that the Arabidopsis SITE-1 PROTEASE (S1P) cleaves endogenous RAPID ALKALINIZATION FACTOR (RALF) propeptides to inhibit plant immunity. This inhibition is mediated by the malectin-like receptor

  4. Pesticides Provoke Endocrine Disruption A Review

    International Nuclear Information System (INIS)

    Aly, M.A.S.

    2006-01-01

    Increasing numbers of environmental chemicals,including pesticides, have the ability to produce endocrine disruption by various mechanisms. such substances may affect hormone secretion from an endocrine gland and may alter the rate of hormone elimination from the body. environmental chemicals may also disrupt regulatory feedback mechanisms that exist between two endocrine organs; or may interact with a hormone receptor either by mimicking or antagonizing the actions of the natural hormone. these chemicals are referred to endocrine disruptive chemicals (EDC's). EDC's act to alter the blood hormone levels or the subsequent action of hormones . the use of radioimmunoassay(RIA) constitutes a superior and unrivalled tool for the determination and quantification of hormones.the endocrine system participates in virtually all important functions of an organism, such as sexual differentiation before birth, sexual maturation during puberty, reproduction in adulthood, growth, metabolism, digestion, cardiovascular function and excretion. hormones are also implicated in the etiology of certain cancers of hormone- dependent tissues, such as those of the breast, uterus, and prostate gland. therefore, endocrine disruption can potentially produce widespread effects. scientists should not stick to the past belief which presumes that pesticides have limited effect on some hormones. A paradigm shift in which a wider vision of understanding of the wholesome complex effects of pesticides on the whole body rather than a narrow limited understanding should take place

  5. 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.

  6. Thyroid effects of endocrine disrupting chemicals.

    Science.gov (United States)

    Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

    2012-05-22

    In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Analysis of recent fuel-disruption experiments

    International Nuclear Information System (INIS)

    Kramer, J.M.; Kraft, T.E.; DiMelfi, R.J.; Fenske, G.R.; Gruber, E.E.

    1982-01-01

    Recent USDOE-sponsored DEH, FGR, and TREAT F series fuel-disruption experiments are analyzed with existing analytical models. The experiments are interpreted and the results used to evaluate the models. Calculations are presented using the FRAS3 fission-gas-behavior code and the DiMelfi-Deitrich fuel-response model

  8. Operational limits and disruptions in ITER

    Energy Technology Data Exchange (ETDEWEB)

    Tsunematsu, T; Mizoguchi, T; Yoshino, R [Japan Atomic Energy Research Inst., Tokyo (Japan); Borrass, K; Engelmann, F; Pacher, G; Pacher, H [Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.). NET Design Team; Cohen, S; Post, D [Princeton Univ., NJ (USA). Plasma Physics Lab.; Hogan, J; Uckan, N A [Oak Ridge National Lab., TN (USA); Krasheninnikov, S; Mukhovatov, V; Parail, V

    1990-12-15

    Detailed knowledge of the operational limits for beta, q and the plasma density will be required for successful and flexible operation of ITER. In this paper, the present data base and guidelines on operational limits and disruptions in the ITER design are presented. 10 refs., 1 fig.

  9. Maternal Characteristics Predicting Young Girls' Disruptive Behavior

    Science.gov (United States)

    van der Molen, Elsa; Hipwell, Alison E.; Vermeiren, Robert; Loeber, Rolf

    2011-01-01

    Little is known about the relative predictive utility of maternal characteristics and parenting skills on the development of girls' disruptive behavior. The current study used five waves of parent- and child-report data from the ongoing Pittsburgh Girls Study to examine these relationships in a sample of 1,942 girls from age 7 to 12 years.…

  10. 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.

  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. 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…

  13. An analysis of recent fuel disruption experiments

    International Nuclear Information System (INIS)

    Kramer, J.M.; Kraft, T.E.; Dimelfi, R.J.; Fenske, G.R.; Gruber, E.E.

    1982-01-01

    Recent USDOE-Sponsored DEH, FGR, and TREAT F series fuel disruption experiments are analyzed with existing analytical models. The experiments are interpreted and the results used to evaluate the models. Calculations are presented using the FRAS3 fission gas behavior code and the DiMelfi-Deitrich fuel response model

  14. 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…

  15. Five disruptive technology directions for 5G

    DEFF Research Database (Denmark)

    Boccardi, Federico; W. Heath Jr., Robert; Lozano, Angel

    2014-01-01

    New research directions will lead to fundamental changes in the design of future fifth generation (5G) cellular networks. This article describes five technologies that could lead to both architectural and component disruptive design changes: device-centric architectures, millimeter wave, massive ...

  16. 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.

  17. Traffic disruption route Einstein near building 170

    CERN Multimedia

    A Lopez - TS/CE

    2005-01-01

    The TS/CE Group informs you that, for the duration of the work at Building 170, there may be some disruption to traffic on route Einstein in the vicinity of Building 170. The work is due to take place from the 14th to 18th February. For more information, please contact 165029. A. Lopez TS/CE

  18. New directions for mating disruption in Wisconsin

    Science.gov (United States)

    Mating Disruption (MD) is an alternative to insecticide for control of three major pests -Sparganthois fruitworm, Cranberry fruitworm and Blackheaded fireworm. MD functions by sending out false plumes of the insect's sex pheromones – this interferes with the insect’s ability to find a mate, preempti...

  19. 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 disruption strategies is very limited. By combining computational modeling and social network analysis with unique criminal network intelligence data from the Dutch Police, we discovered, in contrast to common belief, that criminal networks might even become ‘stronger’, after targeted attacks. On the other hand increased efficiency within criminal networks decreases its internal security, thus offering opportunities for law enforcement agencies to target these networks more deliberately. Our results emphasize the importance of criminal network interventions at an early stage, before the network gets a chance to (re-)organize to maximum resilience. In the end disruption strategies force criminal networks to become more exposed, which causes successful network disruption to become a long-term effort. PMID:24577374

  20. Anomalous periodic disruptions in tokamak plasma

    International Nuclear Information System (INIS)

    Montvai, A.; Tegze, M.; Valyi, I.

    1982-09-01

    Anomalously strong, periodic instabilities were observed in the MT-1 tokamak. Characteristics of these instabilities were partly similar to those of internal disruptions, but there were features making them different from the normal relaxational oscillations. Basic characteristics of the phenomenon were studied with the aid of generally used diagnostics. (author)

  1. 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

  2. Disruptive instabilities in the TBR-1

    International Nuclear Information System (INIS)

    Vannucci, A.

    1987-01-01

    The disruptive instabilities in the TBR-1 tokamak of the Plasma Physics Laboratory of the Institute of Physics-USP were investigated by using surface-barrier detectors and Mirnov magnetic coils, measuring soft X-ray emited by the plasma and poloidal magnetic fluctuations, respectively. Minor and major disruptions, as well sawteeth oscillations, were identified at the TBR-1 discharges, and their main characteristics were studied. Comparing the measured period of the internal disruptions (sawteeth) with the ones expected from scaling laws, good agreements is reached. The measured sawteeth crashes agree with the values expected from the Kadomtsev's model. External helical fields (CHR), corresponding to m/n=2/1 helicity were produced in order to inhibit or criate disruptive instabilities. A strong weakening of the mhd activity, present in the TBR-1 discharges, was clearly detected. The soft X-ray detection system, projected and constructed for this work, was used to obtain the electron temperatures of regions close to the center of the plasma column (T(r=0) ∼ 205 eV and T(r ± 3,8) ∼ 85 eV), using the absorbing foils method. Using the Spitzer formula, Z sub (eff) values were also obtained. (author) [pt

  3. The Structure of Childhood Disruptive Behaviors

    Science.gov (United States)

    Martel, Michelle M.; Gremillion, Monica; Roberts, Bethan; von Eye, Alexander; Nigg, Joel T.

    2010-01-01

    Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) frequently co-occur. Comorbidity of these 2 childhood disruptive behavior domains has not been satisfactorily explained at either a structural or etiological level. The current study evaluated a bifactor model, which allows for a "g" factor in addition to…

  4. Control, pressure perturbations, displacements, and disruptions in highly elongated tokamak plasmas

    International Nuclear Information System (INIS)

    Marcus, F.B.; Hofmann, F.; Tonetti, G.; Jardin, S.C.; Noll, P.

    1989-06-01

    The control and evolution of highly elongated tokamak plasmas with large growth rates are simulated with the axisymmetric, resistive MHD code TSC in the geometry of the TCV tokamak. Pressure perturbations such as sawteeth and externally programmed displacements create initial velocity perturbations which may be stabilized by low power, rapid response coils inside the passively stabilizing vacuum vessel, together with slower shaping coils outside the vessel. Vertical disruption induced voltages and forces on the rapid coils and vessel are investigated, and a model is proposed for an additional vertical force due to poloidal currents. (author) 6 figs., 1 tab., 26 refs

  5. Frequently Asked Questions about Immunizations

    Science.gov (United States)

    ... will be too late for the vaccine to work. The best time to immunize kids is when they're healthy. Can immunizations cause a bad reaction in my child? The most common reactions to vaccines are minor ...

  6. Technique Selectively Represses Immune System

    Science.gov (United States)

    ... Research Matters December 3, 2012 Technique Selectively Represses Immune System Myelin (green) encases and protects nerve fibers (brown). A new technique prevents the immune system from attacking myelin in a mouse model of ...

  7. Rapid Tooling via Stereolithography

    OpenAIRE

    Montgomery, Eva

    2006-01-01

    Approximately three years ago, composite stereolithography (SL) resins were introduced to the marketplace, offering performance features beyond what traditional SL resins could offer. In particular, the high heat deflection temperatures and high stiffness of these highly filled resins have opened the door to several new rapid prototyping (RP) applications, including wind tunnel test modelling and, more recently, rapid tooling.

  8. The mass disruption of Jupiter Family comets

    Science.gov (United States)

    Belton, Michael J. S.

    2015-01-01

    I show that the size-distribution of small scattered-disk trans-neptunian objects when derived from the observed size-distribution of Jupiter Family comets (JFCs) and other observational constraints implies that a large percentage (94-97%) of newly arrived active comets within a range of 0.2-15.4 km effective radius must physically disrupt, i.e., macroscopically disintegrate, within their median dynamical lifetime. Additional observational constraints include the numbers of dormant and active nuclei in the near-Earth object (NEO) population and the slope of their size distributions. I show that the cumulative power-law slope (-2.86 to -3.15) of the scattered-disk TNO hot population between 0.2 and 15.4 km effective radius is only weakly dependent on the size-dependence of the otherwise unknown disruption mechanism. Evidently, as JFC nuclei from the scattered disk evolve into the inner Solar System only a fraction achieve dormancy while the vast majority of small nuclei (e.g., primarily those with effective radius <2 km) break-up. The percentage disruption rate appears to be comparable with that of the dynamically distinct Oort cloud and Halley type comets (Levison, H.F., Morbidelli, A., Dones, L., Jedicke, R., Wiegert, P.A., Bottke Jr., W.F. [2002]. Science 296, 2212-2215) suggesting that all types of comet nuclei may have similar structural characteristics even though they may have different source regions and thermal histories. The typical disruption rate for a 1 km radius active nucleus is ∼5 × 10-5 disruptions/year and the dormancy rate is typically 3 times less. We also estimate that average fragmentation rates range from 0.01 to 0.04 events/year/comet, somewhat above the lower limit of 0.01 events/year/comet observed by Chen and Jewitt (Chen, J., Jewitt, D.C. [1994]. Icarus 108, 265-271).

  9. Perceptual consequences of disrupted auditory nerve activity.

    Science.gov (United States)

    Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

    2005-06-01

    Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique

  10. Ocular surface immunity: Homeostatic mechanisms and their disruption in dry eye disease

    OpenAIRE

    Barabino, Stefano; Chen, Yihe; Chauhan, Sunil Kumar; Dana, Reza

    2012-01-01

    The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others...

  11. Clonal Selection Based Artificial Immune System for Generalized Pattern Recognition

    Science.gov (United States)

    Huntsberger, Terry

    2011-01-01

    The last two decades has seen a rapid increase in the application of AIS (Artificial Immune Systems) modeled after the human immune system to a wide range of areas including network intrusion detection, job shop scheduling, classification, pattern recognition, and robot control. JPL (Jet Propulsion Laboratory) has developed an integrated pattern recognition/classification system called AISLE (Artificial Immune System for Learning and Exploration) based on biologically inspired models of B-cell dynamics in the immune system. When used for unsupervised or supervised classification, the method scales linearly with the number of dimensions, has performance that is relatively independent of the total size of the dataset, and has been shown to perform as well as traditional clustering methods. When used for pattern recognition, the method efficiently isolates the appropriate matches in the data set. The paper presents the underlying structure of AISLE and the results from a number of experimental studies.

  12. Rapid improvement teams.

    Science.gov (United States)

    Alemi, F; Moore, S; Headrick, L; Neuhauser, D; Hekelman, F; Kizys, N

    1998-03-01

    Suggestions, most of which are supported by empirical studies, are provided on how total quality management (TQM) teams can be used to bring about faster organizationwide improvements. Ideas are offered on how to identify the right problem, have rapid meetings, plan rapidly, collect data rapidly, and make rapid whole-system changes. Suggestions for identifying the right problem include (1) postpone benchmarking when problems are obvious, (2) define the problem in terms of customer experience so as not to blame employees nor embed a solution in the problem statement, (3) communicate with the rest of the organization from the start, (4) state the problem from different perspectives, and (5) break large problems into smaller units. Suggestions for having rapid meetings include (1) choose a nonparticipating facilitator to expedite meetings, (2) meet with each team member before the team meeting, (3) postpone evaluation of ideas, and (4) rethink conclusions of a meeting before acting on them. Suggestions for rapid planning include reducing time spent on flowcharting by focusing on the future, not the present. Suggestions for rapid data collection include (1) sample patients for surveys, (2) rely on numerical estimates by process owners, and (3) plan for rapid data collection. Suggestions for rapid organizationwide implementation include (1) change membership on cross-functional teams, (2) get outside perspectives, (3) use unfolding storyboards, and (4) go beyond self-interest to motivate lasting change in the organization. Additional empirical investigations of time saved as a consequence of the strategies provided are needed. If organizations solve their problems rapidly, fewer unresolved problems may remain.

  13. Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

    Science.gov (United States)

    Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

    2015-06-23

    F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

  14. Phenomenology of high density disruptions in the TFTR tokamak

    International Nuclear Information System (INIS)

    Fredrickson, E.D.; McGuire, K.M.; Bell, M.G.

    1993-01-01

    Studies of high density disruptions on TFTR, including a comparison of minor and major disruptions at high density, provide important new information regarding the nature of the disruption mechanism. Further, for the first time, an (m,n)=(1,1) 'cold bubble' precursor to high density disruptions has been experimentally observed in the electron temperature profile. The precursor to major disruptions resembles the 'vacuum bubble' model of disruptions first proposed by B.B. Kadomtsev and O.P. Pogutse (Sov. Phys. - JETP 38 (1974) 283). (author). Letter-to-the-editor. 25 refs, 3 figs

  15. Vitamin E, immunity, and infection

    Science.gov (United States)

    A normally functioning immune system is critical for the body to fight and eliminate invading pathogens from the environment. On the other hand, the immune system also protects the body from internal risks such as neoplasia growing within and autoimmune responses that attack self. The immune system ...

  16. NKT Cell Networks in the Regulation of Tumor Immunity

    Science.gov (United States)

    Robertson, Faith C.; Berzofsky, Jay A.; Terabe, Masaki

    2014-01-01

    CD1d-restricted natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic, and myeloid lineage cells, as well as adaptive populations, especially CD8+ and CD4+ T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host’s ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting. PMID:25389427

  17. NKT cell networks in the regulation of tumor immunity.

    Science.gov (United States)

    Robertson, Faith C; Berzofsky, Jay A; Terabe, Masaki

    2014-01-01

    CD1d-restricted natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic, and myeloid lineage cells, as well as adaptive populations, especially CD8(+) and CD4(+) T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host's ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting.

  18. NKT cell networks in the regulation of tumor immunity

    Directory of Open Access Journals (Sweden)

    Faith C Robertson

    2014-10-01

    Full Text Available CD1d-restricted natural killer T (NKT cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic and myeloid lineage cells, as well as adaptive populations, especially CD8+ and CD4+ T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host’s ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting.

  19. The dynamics of naturally acquired immunity to Plasmodium falciparum infection.

    Directory of Open Access Journals (Sweden)

    Mykola Pinkevych

    Full Text Available Severe malaria occurs predominantly in young children and immunity to clinical disease is associated with cumulative exposure in holoendemic settings. The relative contribution of immunity against various stages of the parasite life cycle that results in controlling infection and limiting disease is not well understood. Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity. We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites. We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains. Analysis and modelling of malaria infection dynamics and naturally acquired immunity with age provides important insights into what mechanisms of immune control may be harnessed by malaria vaccine strategists.

  20. Engineering synthetic vaccines using cues from natural immunity

    Science.gov (United States)

    Irvine, Darrell J.; Swartz, Melody A.; Szeto, Gregory L.

    2013-11-01

    Vaccines aim to protect against or treat diseases through manipulation of the immune response, promoting either immunity or tolerance. In the former case, vaccines generate antibodies and T cells poised to protect against future pathogen encounter or attack diseased cells such as tumours; in the latter case, which is far less developed, vaccines block pathogenic autoreactive T cells and autoantibodies that target self tissue. Enormous challenges remain, however, as a consequence of our incomplete understanding of human immunity. A rapidly growing field of research is the design of vaccines based on synthetic materials to target organs, tissues, cells or intracellular compartments; to co-deliver immunomodulatory signals that control the quality of the immune response; or to act directly as immune regulators. There exists great potential for well-defined materials to further our understanding of immunity. Here we describe recent advances in the design of synthetic materials to direct immune responses, highlighting successes and challenges in prophylactic, therapeutic and tolerance-inducing vaccines.